RECEPTOR-TARGETED PROTEIN TOXINS FOR BRAIN TUMOR THERAPY

  • Kung, Hsing-Jien (PI)
  • Mapstone, Timothy (PI)
  • Fenstermaker, Robert (PI)
  • Landis, Dennis (PI)
  • Large, Thomas (PI)
  • Berger, Nathan (PI)

Project: Research project

Project Details

Description

This proposal is to develop a Brain Tumor Research Center at Case Western
Reserve University and University Hospitals of Cleveland whose central
focus will be the development application of membrane targeted, peptide
toxins to improve therapy for malignant brain tumors. The proposal
constitutes a synergistic, interdisciplinary, interaction of the
clinical, scientific and organizational expertise of physicians and
scientists from the Departments of Neurosurgery, Neurology,
Neurosciences, Molecular Biology, Medicine, Pediatrics and the Ireland
Cancer Center at University Hospitals of Cleveland and Case Western
Reserve University. Project 1 will examine the fundamental role of the
epidermal growth factor receptor (EGF-R) and the associated signal
transduction processes in establishing and maintaining the transformed
state in gliomas. Project 2 will examine the role of neurotrophins and
the trk family of protooncogenes for their role in growth promotion and
establishment of the malignant state in primitive neuroectodermal tumors
and astrocytomas. Project 3 will analyze human brain tumors for
activation of a specific series of oncogenes including PDGF, Gli and
acidic and basic FGF, postulated to be involved in promoting glial cell
proliferation. This project will also establish brain tumor derived,
human cell lines and test representative samples to evaluate the growth
regulating effect of interfering with function and/or expression of these
oncogenes. Project 4 will examine the in vitro and in vivo cytotoxic
effects of a series of fusion protein constructs, composed of epidermal
growth factor (EGF) fused with bacterial exotoxins, on human brain tumors
bearing the EGF receptor. Project 5 will develop and test monoclonal
antibodies with specificity for malignant astrocyte determinants for
their cytotoxic effects on brain tumors. The program will promote the
multidisciplinary clinical management of patients with brain tumors and
will serve to foster technology transfer from research lab to clinical
trials.
StatusFinished
Effective start/end date4/1/933/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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