Physicians

Gregory W Canute, M.D.

Associate Professor, Neurosurgery
605 Jacobsen Hall
Upstate Medical University
750 East Adams Street
Syracuse, NY 13210
(315) 464-5513

Lab/Professional Web Site

Education and Clinical Training

M.D.: 1991, University of Michigan Medical School
Internship: Surgery, 1992, University Hospital, SUNY Health Science Center at Syracuse
Residency: Neurosurgery, 1998, University Hospital, SUNY Upstate Medical University

Clinical Specialty

Neurological Surgery

Clinical Department/Section Affiliations

Neurosurgery/Brain Tumors
Neurosurgery/Radiosurgery

Clinical Interests

Brain Tumors Radiosurgery (Gamma Knife)

Research Program and Department Affiliations

Biomedical Sciences Program
Neuroscience Program
Neurosurgery

Research Interests

Genetics and Gene Therapy of Brain Tumors

Research Abstract

Brain Tumor Research Laboratory

The brain tumor research laboratory has been studying the molecular genetics of glioblastoma multiforme (GBMs) with the goal of developing new therapeutic agents against this malignant brain tumor. Two lines of research have been the focus of our laboratory; exploring mechanisms to decrease tumor cell growth and increase tumor cell death.

The epidermal growth factor receptor (EGFR) has been the major focus of the laboratory since 1993. Previously using hydroxyurea (1,2) we have decreased cell proliferation through the EGFR pathway by inhibiting the ribonucleotide reductase enzyme. Currently our research interest includes using Cetuximab(Erbitux,C225), a monoclonal antibody against EGFR (3,4) against GBM. Cetuximab attacks the EGFR pathway by blocking access of essential growth factors to the cells and decreasing the rate of growth, survival and ability to form blood vessels. We have also be tested Cetuximab in combination with standard radiation and chemotherapy agents to determine if their combined effects are better than individual treatments (4).

In another line of research our laboratory is studying the Fas/Fas ligand system in GBMs. This system has been shown to play an essential role in regulating cell death within the immune system. In initial studies we have shown that GBMs have both Fas and FasL and when the Fas receptor is upregulated there is an increases in cell death(5-7). Currently, experiments are being designed to elucidate the potential use of this "death " receptor system for anti-GBM therapy.

Preclinical results from the brain tumor research laboratory have evolved into clinical trials including the use of Hydroxyurea, as well as the standard GBM therapy, BCNU, combined with Trental. We are currently designing a Phase I clinical study for using Cetuximab in patients with relapsed GBM.

Selected References

1. Canute GW, Winfield JA, Longo JA, Longo SL, Nevaldine B, Hahn PJ: Hydroxyurea accelerates the loss of the epidermal growth factor receptor genes amplified as double-minute chromosomes in human glioblastoma multiforme. Neurosurg 39:976-983, 1996.

2. Canute GW, Longo SL, Longo JA, Shetler MM, Coyle TE, Winfield JA, Hahn PJ: The hydroxyurea-induced loss of double-minute chromosomes containing amplified epidermal growth factor receptor genes reduces the tumorigenicity of human glioblastoma multiforme. Neurosurg 42:609-616, 1998.

3. Eller JL, Longo SL, Canute GW: The activity of anti-EGFR monoclonal antibody C225 against glioblastoma multiforme. Neurosurg 51:1005-1014, 2002.

4. Eller JL, Longo SL, Kyle MM, Bassano D, Hicklin DJ, Canute GW: Anti-EGFR monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo. Neurosurg 56:155-162, 2005.

5. Frankel B, Longo SL, Canute GW: Soluble Fas-ligand (sFasL) in human astrocytoma cyst fluid is cytotoxic to T-cells: another potential means of immune evasion. J Neuro-Oncol 48:21-26, 2000.

6. Frankel B, Longo SL, Kyle M, Canute GW, Ryken TC: Tumor Fas(APO-1/CD95) up-regulation in high-grade astrocytomas results in increased apoptosis and survival times for rats with intracranial malignant gliomas. Neurosurg 49:168-175, 2001.

7. Frankel B, Longo SL, Leach C, Canute GW, Ryken TC: Apoptosis and survival in high-grade astrocytomas as related to tumor Fas expression. J Neuro-Oncol 59:27-34, 2002.

Publications - link to PubMed

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This profile was last updated on 09/29/2008

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http://www.upstate.edu/practice/neurosurgery/physicians/index.php?ID=canuteg

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