• Feuerstein, Burt G.F. (PI)
  • Talcott, Ronald (PI)
  • Rosenblum, Mark (PI)
  • Marton, Lawrence (PI)
  • Levin, Victor (PI)
  • Wilson, Charles (PI)
  • Berger, Mitchel S. (PI)
  • Prados, Michael (PI)
  • Fike, John (PI)
  • Israel, Mark (PI)
  • Deen, Dennis (PI)
  • Bodell, William (PI)
  • Chan, Pak (PI)

Project: Research project

Grant Details


Primary brain tumors were responsible for 11,800 deaths in the US in 1992.
Brain tumors are second only to leukemia as the leading cause of cancer
death among children younger than 15 yr. of age, and the 4th most frequent
cause among men 15-35 yr. old. While fewer women are afflicted overall,
they made up 46% of the estimated 16,900 patients with new brain tumors
diagnosed in 1992. If the many other forms of cancer that metastasize to
the brain are added, the number of patients with brain tumors rises
significantly, and the incidence of these lesions in people over 65 yr. of
age is increasing. Surgery is the primary treatment for brain malignancy
but for most patients, only subtotal resection of tumor can be achieved;
adjuvant treatment is needed to impede tumor regrowth. The Brain Tumor
Research Center (BTRC) has developed into a major treatment center for
patients with tumors of the brain. The BTRC's long-term objective is to
cure malignant brain tumors. To achieve it requires us to understand the
biology of the disease and attack it at the basis of underlying genetic
deficiencies. In the short term, our goals are to improve existing brain
tumor therapies and develop new and more effective therapeutic approaches.
This proposal targets radiation, the most effective treatment for
malignant lesions after surgery, and glioblastoma multiforme (GBM), the
most aggressive malignant lesion in the brain. Our overall hypothesis is
that the clinical results of radiation therapy can be improved markedly by
refining existing radiation therapy protocols, by identifying tumors that
are resistant to radiation before patients undergo radiation therapy, and
by ameliorating or overcoming cellular resistance to radiation. The interrelated projects that compose our research program are integrated
in a single theme: escalation of clinical efficacy of radiation therapy
for GBM to the maximum level possible within the next 5 yr. Prados'
project includes the clinical trials for adult patients. Feuerstein and
Deen will identify patients with radiation-resistant GBM at surgery so
that alternative therapies can be considered. Feuerstein will provide
important genetic information for categorizing brain tumors. Bodell will
determine the relationship between radiation resistance and resistance to
nitrosoureas; it will identify those patients whose tumors will be
refractory to nitrosourea therapy alone. Fike will define the critical
radiation dose-volume relationships for radiosurgery, so that clinical
treatments provided by using this modality can be optimized for safety and
efficacy. Chan will define the role that oxidative stress plays in
radiation-induced injury to endothelial cells, the critical dose-limiting
tissues for therapy. Israel will investigate the genetic determinants and
biochemical pathways involved in cell cycle delays that are important in
overall cellular radiation-induced damage.
Effective start/end date4/1/799/30/00


  • National Institutes of Health


  • Medicine(all)


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