Browsing by Author "McMullen, Kevin"

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    Phase II Study of Ginkgo Biloba in Irradiated Brain Tumor Patients: Effect on Cognitive Function, Quality of Life, and Mood
    (Springer, 2012) Attia, Albert; Rapp, Stephen R.; Case, L. Doug; D’Agostino, Ralph; Lesser, Glenn; Naughton, Michelle; McMullen, Kevin; Rosdhal, Robin; Shaw, Edward G.; Radiation Oncology, School of Medicine
    Ginkgo biloba has been reported to improve cognitive function in older adults and patients with Alzheimer's disease and multi-infarct dementia. We conducted an open-label phase II study of this botanical product in symptomatic irradiated brain tumor survivors. Eligibility criteria included: life expectancy ≥30 weeks, partial or whole brain radiation ≥6 months before enrollment, no imaging evidence of tumor progression in previous 3 months, or stable or decreasing steroid dose, and no brain tumor treatment planned while on study. The Ginkgo biloba dose was 120 mg/day (40 mg t.i.d.) for 24 weeks followed by a 6-week washout period. Assessments performed at baseline, 12, 24 (end of treatment), and 30 weeks (end of washout) included KPS, Functional Assessment of Cancer Therapy-Brain (FACT-Br), Profile of Mood States, Mini-Mental Status Exam, Trail Making Test Parts A (TMT-A) and B (TMT-B), Digit Span Test, Modified Rey Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II, and the F-A-S Test. Results: Of the 34 patients enrolled on study, 23 (68 %) completed 12 weeks of treatment and 19 (56 %) completed 24 weeks of treatment. There were significant improvements at 24 weeks in: executive function (TMT-B) (p = 0.007), attention/concentration (TMT-A) (p = 0.002), and non-verbal memory (ROCF-immediate/delayed recall) (p = 0.001/0.002), mood (p = 0.002), FACT-Br subscale (p = 0.001), and the FACT physical subscale (p = 0.003). Conclusions: Some improvement in quality of life and cognitive function were noted with Ginkgo biloba. However, treatment with Ginkgo biloba was associated with a high dropout rate.
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    Radiation therapy generates platelet-activating factor agonists
    (Impact Journals, 2016-04-12) Sahu, Ravi P.; Harrison, Kathleen A.; Weyerbacher, Jonathan; Murphy, Robert C.; Konger, Raymond L.; Garrett, Joy Elizabeth; Chin-Sinex, Helen Jan; Johnston II., Michael Edward; Dynlacht, Joseph R.; Mendonca, Marc; McMullen, Kevin; Li, Gengxin; Spandau, Dan F.; Travers, Jeffrey B.; Department of Dermatology, IU School of Medicine
    Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens.