Project Funding Details

Purpose/Specific Aims: The purpose of this research program is to identify biobehavioral mechanisms that affect treatment outcomes in patients with a primary malignant brain tumor (PMBT). As a first step, the specific aim of this study is to examine the relationships among psychoneurological (PN) symptoms, markers of glial activation [levels of matrix metalloproteinase (MMP)-2, and MMP-9] and quality of life (QOL) in individuals with PMBT over time. Data will be collected at the time of tumor resection and at 3 and 6-months following tumor resection. A secondary aim will be to compare markers of glial activation in tumor tissue to blood at the time of tumor resection.
Rationale/ Significance of Study: Of the 43,000 individuals diagnosed with a primary malignant brain tumor (PMBT) each year in the United States, over 75% will experience psychoneurological (PN) symptoms, such as depression, anxiety, fatigue, pain, and sleep disturbances, that significantly impair cognitive and physical functioning, quality of life (QOL) and possibly, survival time. A growing body of research indicates that PN symptoms may be linked with underlying biological phenomena, particularly inflammatory activation regulated by glial cells (astrocytes and microglia). Glial activation with increased release of MMP-2 and MMP-9 may also affect the onset and progression of PN symptoms by (1) altering the brain microenvironment and (2) impairing the function of astrocytes in modulating neuronal activity and synaptic transmission.
Conceptual or Theoretical Framework: The proposed project represents a biobehavioral approach to understanding the manifestation of symptoms in persons with a PMBT by examining the relationships psychological, neurological, and biological variables.
Main Research Variable(s): Psychoneurological Symptoms, MMP-2, MMP-9, Quality of Life Design: This is a longitudinal exploratory study.
Setting: VCU’s Massey Cancer Center (MCC), the primary referral center for patients with a brain tumor in the Richmond vicinity, will be used for subject recruitment and data collection.
Sample: The study sample will include 36 participants with a diagnosis of a PMBT who will be undergoing surgery for tumor biopsy or resection. Male and female adults from all ethnic and racial backgrounds will be recruited.
Methods: Study questionnaires (MD Anderson Symptom Inventory, Beck Depression Inventory, Medical Outcomes SF-36 Health Survey) will be administered and a blood specimen (5 mL) will be collected at the time of surgical resection and 3- and 6-months following tumor resection. Tumor tissue will be collected during surgical resection. The specimens will be placed on ice and transported directly to the CBCR laboratory for processing, storage, and analysis for levels of MMP-2 and MMP-9 by ELISA.
Implications for Practice: The proposed study will provide an essential first step toward identifying biobehavioral mechanisms that affect treatment outcomes in persons with a PMBC, and may provide empirical data on whether targeting of glial activation should be examined as a potential method to improve PN symptom management and QOL. The results may also help to identify biological factors that can be used to predict PN symptoms over the disease trajectory, which would be informative for patients as they are making decisions about their treatment options.