The purpose of this study is:

1. To learn if (MMP-2, MMP-9 and NGAL) which are substances found in blood and urine associated with tumors, can be used as tumor markers in the management and treatment of glioblastoma.
2. To study the relationship between MMP-2, MMP-9 and NGAL with quality of life and disease symptoms.

Matrix metalloproteinases (MMP) -2 and -9 belong to a multigene family of degradative enzymes implicated in the neoangiogenesis required for tumor growth. In the central nervous system (CNS), MMP-2, MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL) are overexpressed in orthotopic models and also in human brain tumor specimens. Furthermore, serum and urinary levels of these markers have been shown to correlate with the presence and status of brain tumors in all types of primary brain tumors. A major challenge in the treatment of primary brain tumors is the dependence on magnetic resonance imaging (MRI) to differentiate disease progression from treatment-related change. This is particularly challenging in glioblastomas (GBM) where multimodality therapy with radiation and chemotherapy is commonly used and can lead to pseudoprogression and treatment-related tissue necrosis, both of which can masquerade as true tumor progression. Often we are faced with the decision to treat based on imaging findings alone or to recommend that patients have another invasive surgery. We hypothesize that MMP-2, MMP-9 and NGAL will: 1) be detected on tumor tissue by immunohistochemistry and not on non-tumor (epilepsy) brain tissue, 2) parallel the course of disease in the urine and/or serum of patients and 3) remain unchanged in the event of pseudoprogression and treatment related imaging changes. Quality of life, patient symptoms, and cognitive function are vitally important in patients with GBM. Quality of life and selected symptoms will also be assessed and correlated with serum and urine biomarkers. We hope to confirm the utility of MMP-2, MMP-9 and NGAL in the management of GBM.

Inclusion Criteria:

1. Subjects scheduled for a surgical excision or biopsy as ordered by his/her clinic or inpatient physician for epilepsy OR subjects newly diagnosed with high grade (grade IV) glioma (The performance of this procedure will be under standard of care surgical guidelines.)

   • non-tumor tissue controls from subjects undergoing surgery for epilepsy
   • tumor tissue from subjects undergoing surgery for grade IV glioma

2. Epilepsy subject identified as a control undergoing surgery must willingly provide pre-op and post-op serum and urine samples for research

3. GMB subject must willingly provide blood and urine samples pre-op and post-op as well as blood and urine samples for research and QOL measurements taken at protocol specific time points

4. GBM subject plans to receive clinical care visits which coincide with MRIs and/or with a change in symptoms and any secondary surgical resections and/or biopsies solely at UNMC/TNMC

5. Subjects must willingly give signed informed consent

6. Age 19 years or older (the age of consent in Nebraska)

7. Women must not be pregnant due to teratogenic effects of MRI

Exclusion Criteria:

1. Inability to fulfill the requirements of the protocol

2. No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study

3. Known to be positive for HIV or infectious hepatitis, type A, B or C or active Hepatitis

4. Subjects newly diagnosed with high grade (grade IV) glioma (GBM) unable to be followed by MRI due to

   • Pacemaker
   • Chronic kidney disease stage 3-5 (Glomerular Filtration Rate <60)
   • Unable to lay flat for 90 minutes
   • Any metallic foreign body not approved for MRI
   • Known hypersensitivity to Gadolinium contrast or other required for MRI

Subjects scheduled for a surgical excision or biopsy as ordered by his/her clinic or inpatient physician for epilepsy OR subjects newly diagnosed with high grade (grade IV) glioma