The Alteration of Survivin Expression and Localization in Glioblastoma Cell Lines in Response to Exposure to Chemical and Physical Agents
Shefalika Prasad(1,2) and Michael J. Ciesielski1, Ph.D.(1)
1 Department of Neuro-Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263
2 Clarence High School, Clarence, NY & Roswell Summer Research Internship Program in Cancer Science
ABSTRACT SUMMARY:
Treatment for malignant gliomas includes immunotherapy targeting specific intercellular proteins. Survivin, an intercellular protein, is currently being studied and used for vaccine development. This study serves to elucidate the effects of other treatment modalities used in gliomas on the expression and localization of survivin in the tumor cell. This will reveal potential interactions of these agents with survivin – targeted immunotherapy. GL261 Glioma cell line in tissue culture was challenged by: heat shock, cold, temozolomide (100μg/ml), radiation (2Gy), and radiofrequency (RF) exposure (200khz). Survivin expression and localization was screened by immunofluorescence (IF) microscopy. Each treatment condition led to distinct subcellular alterations of survivin levels and localization. Temozolomide, heat, and radiation produced capping of the protein on one side of the cells, however, heat and radiation additionally caused endonuclear localization and temozolomide additionally caused an increase in overall expression. Cold resulted in localization of survivin in both the cytoplasmic and nuclear membranes. Most noticeable, RF significantly increased the survivin expression and caused membrane and vacuole localization.
Making of the Radio Frequency Generator
In longer dosage cells, exosomal budding was also observed. Since none of the agents used decreases survivin expression, immunotherapy can be used in conjunction with high intensity focused ultrasound, cryotherapy, chemotherapy, radiation, and Novocure™. Increased survivin expression with RF might yield synergistic effects. Further research will include effects of these agents on other cell lines, and testing different frequencies of RF.
Abstract
Received: 10 January 2017 /Accepted: 31 January 2017
# Springer-Verlag Berlin Heidelberg 2017
Purpose The study was designed to evaluate the cumulative dose exposure of brain and hippocampus following multiple stereotactic radiosurgery (SRS) procedures on a single patient. Materials and methods Ninety-four patients who received at least two SRS treatments were evaluated. Their SRS dose plans were summated to obtain dose volume parameters. Hippocampal structures were delineated, in addition to segmentation of the brain. Results A total of 267 treatments were delivered to 94 patients. The number of SRS procedures per patient varied from 2 to 7 (mean = 2.8), and the total number of lesions treated in a given patient overmultiple treatments varied from 2 to 70 (mean = 11).
The interval between the first and last SRS treatments varied from 1 to 79months (mean = 16.2 months). Themean prescription dose was 16.7 Gy prescribed to isodose lines from 40 to 95%. The mean coverage, selectivity, Paddick conformity, and gradient index were 99.6%, 79%, 0.57, and 2.74, respectively. The mean summated dose delivered to the whole brain over the course of multiple treatments was 5.11 Gy. The hippocampal mean dose after summation was 2.95 Gy. Patients with plan PCIs averaging below the mean value of 0.57 had higher V8, V10, V12, andV15 values for a given total tumor volumewhen compared with more conformal plans (PCI > 0.57). Conclusions Repeat SRS delivered low cumulative doses to the brain and hippocampus with the lowest normal brain volumes irradiated in highly conformal plans.
Keywords SRS . Brain protection . Brain metastasis . Radiosurgery
