Glioblastoma multiforme (GBM) is the most malignant, incurable brain tumor and most patients die in less than a year. Tumor progression is accompanied by elevated eicosanoid production and this is thought to be responsible for the peritumoral brain edema that develops in these patients. The glucocorticoids currently used to treat brain edema are associated with numerous side effects. The long-term goal of the proposed research is to reduce the morbidity and mortality of these patients and to improve the quality of life. We have provided evidence that 5-1ipoxygenase (5-LO) is elevated in most GBM samples and hypothesize that oxidation of arachidonic acid (AA) by the elevated 5-LO is responsible for the increased 5-LO eicosanoid production and peritumoral brain edema in these patients. The central hypothesis of this application is that a diet low in fatty acid substrates of 5-LO, together with an herbal preparation that contains 5-LO inhibitors, will produce measurable, biologically meaningful decreases in 5-LO eicosanoid production and brain edema that will be associated with improved survival and quality of life in patients with GBM. We propose a trial in which 70 patients will be randomized to control and intervention groups. The intervention will consist of a low-fat vegan diet with severely restricted dietary sources of co-6 polyunsaturated fatty acids, linoleic acid and AA (this is expected to decrease the availability of AA in tumors) and Boswelic, a preparation of frankincense (Boswellia serrata), that we expect will specifically suppress the production of the 5-LO eicosanoids that are generated when 5-LO oxidizes AA.
The Specific Aims are to determine whether this 2-pronged approach to decreasing 5-LO eicosanoid production (1) reduces peritumoral brain edema in patients with GBM, (2) prolongs survival, and (3) improves quality of life. The proposed study is significant in that, to our knowledge, no one has let evaluated either the potential benefits of a dietary approach to inhibiting eicosanoid production of potential benefits of a standardized B. serrata herbal product that contains naturally occurring 5-LC inhibitors in patients with GBM Incorporation of a combination of dietary and herbal approaches as an adjuvant to standard care is likely to empower patients with this incurable brain tumor, even if it fails to extend survival. It would allow patients to """"""""take charge"""""""" of their lives, which is itself a life enhancing experience and a major reason whv patients with GBM frequentlv use CAM therapies. ? ?
| Nathoo, Narendra; Prayson, Richard A; Bondar, Judy et al. (2006) Increased expression of 5-lipoxygenase in high-grade astrocytomas. Neurosurgery 58:347-54; discussion 347-54 |
