All Publications

  • Review: therapeutic approaches for circadian modulation of the glioma microenvironment. Frontiers in oncology Nettnin, E. A., Nguyen, T., Arana, S., Barros Guinle, M. I., Garcia, C. A., Gibson, E. M., Prolo, L. M. 2023; 13: 1295030


    High-grade gliomas are malignant brain tumors that are characteristically hard to treat because of their nature; they grow quickly and invasively through the brain tissue and develop chemoradiation resistance in adults. There is also a distinct lack of targeted treatment options in the pediatric population for this tumor type to date. Several approaches to overcome therapeutic resistance have been explored, including targeted therapy to growth pathways (ie. EGFR and VEGF inhibitors), epigenetic modulators, and immunotherapies such as Chimeric Antigen Receptor T-cell and vaccine therapies. One new promising approach relies on the timing of chemotherapy administration based on intrinsic circadian rhythms. Recent work in glioblastoma has demonstrated temporal variations in chemosensitivity and, thus, improved survival based on treatment time of day. This may be due to intrinsic rhythms of the glioma cells, permeability of the blood brain barrier to chemotherapy agents, the tumor immune microenvironment, or another unknown mechanism. We review the literature to discuss chronotherapeutic approaches to high-grade glioma treatment, circadian regulation of the immune system and tumor microenvironment in gliomas. We further discuss how these two areas may be combined to temporally regulate and/or improve the effectiveness of immunotherapies.

    View details for DOI 10.3389/fonc.2023.1295030

    View details for PubMedID 38173841

    View details for PubMedCentralID PMC10762863

  • Behavior of glioblastoma brain tumor stem cells following a suborbital rocket flight: reaching the "edge" of outer space. NPJ microgravity Garcia, C. A., Suárez-Meade, P., Brooks, M., Bhargav, A. G., Freeman, M. L., Harvey, L. M., Quinn, J., Quiñones-Hinojosa, A. 2023; 9 (1): 92


    The emerging arena of space exploration has created opportunities to study cancer cell biology in the environments of microgravity and hypergravity. Studying cellular behavior in altered gravity conditions has allowed researchers to make observations of cell function that would otherwise remain unnoticed. The patient-derived QNS108 brain tumor initiating cell line (BTIC), isolated from glioblastoma (GBM) tissue, was launched on a suborbital, parabolic rocket flight conducted by EXOS Aerospace Systems & Technologies. All biologicals and appropriate ground controls were secured post-launch and transported back to our research facility. Cells from the rocket-flight and ground-based controls were isolated from the culture containers and expanded on adherent flasks for two weeks. In vitro migration, proliferation, and stemness assays were performed. Following cell expansion, male nude mice were intracranially injected with either ground-control (GC) or rocket-flight (RF) exposed cells to assess tumorigenic capacity (n = 5 per group). Patient-derived QNS108 BTICs exposed to RF displayed more aggressive tumor growth than the GC cells in vitro and in vivo. RF cells showed significantly higher migration (p < 0.0000) and stemness profiles (p < 0.01) when compared to GC cells. Further, RF cells, when implanted in vivo in the brain of rodents had larger tumor-associated cystic growth areas (p = 0.00029) and decreased survival (p = 0.0172) as compared to those animals that had GC cells implanted.

    View details for DOI 10.1038/s41526-023-00341-9

    View details for PubMedID 38110398

    View details for PubMedCentralID PMC10728190

  • BIOPROCESSING OF SURGICAL PEDIATRIC BRAIN TUMOR SPECIMENS FOR GENOME-GUIDED PERSONALIZED DRUG TESTING Nasajpour, E., Tran, C., Garcia, C., Lyle, G., Guinle, M., Bagley, B. A., Lancero, H., Gibson, E. E., Schouten, T., Mahaney, K., Vogel, H., Learned, K., Vaske, O., Grant, G. A., Prolo, L. M., Petritsch, C. K. OXFORD UNIV PRESS INC. 2023
  • BIOPROCESSING OF SURGICAL PEDIATRIC BRAIN TUMOR SPECIMENS FOR GENOME-GUIDED PERSONALIZED DRUG TESTING Nasajpour, E., Lyle, G., Lancero, H., Garcia, C., Learned, K., Gibson, E., Tran, C., Schouten, T., Vogel, H., Mahaney, K., Prolo, L., Vaske, O., Grant, G., Petritsch, C. OXFORD UNIV PRESS INC. 2022: 232
  • 5-Aminolevulinic Acid Imaging of Malignant Glioma. Surgical oncology clinics of North America Li, G., Rodrigues, A., Kim, L., Garcia, C., Jain, S., Zhang, M., Hayden-Gephart, M. 2022; 31 (4): 581-593


    High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the extent of resection has been associated with improving progression-free survival and overall survival by several months. The introduction of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery has allowed surgeons to better differentiate between neoplastic tissue and normal tissue, thus achieving greater extent of resection. The development of new intraoperative imaging modalities in combination with 5-ALA may provide additional benefits for glioma patients.

    View details for DOI 10.1016/j.soc.2022.06.002

    View details for PubMedID 36243495

  • Development of an Integrated Risk Scale for Prediction of Shunt Placement After Neonatal Intraventricular Hemorrhage Jin, M. C., Parker, J. J., Rodrigues, A., Colon, G. R., Garcia, C. A., Mahaney, K. B., Grant, G. A., Prolo, L. M. OXFORD UNIV PRESS INC. 2022: 37-38
  • Development of an integrated risk scale for prediction of shunt placement after neonatal intraventricular hemorrhage. Journal of neurosurgery. Pediatrics Jin, M. C., Parker, J. J., Rodrigues, A. J., Ruiz Colón, G. D., Garcia, C. A., Mahaney, K. B., Grant, G. A., Prolo, L. M. 2022: 1-10


    Neonatal intraventricular hemorrhage (IVH) is a major cause of mortality and morbidity, particularly following premature birth. Even after the acute phase, posthemorrhagic hydrocephalus is a long-term complication, frequently requiring permanent ventriculoperitoneal shunt (VPS) placement. Currently, there are no risk classification methods integrating the constellation of clinical data to predict short- and long-term prognosis in neonatal IVH. To address this need, the authors developed a two-part machine learning approach for predicting short- and long-term outcomes after diagnosis of neonatal IVH. Integrating both maternal and neonatal characteristics, they developed a binary classifier to predict short-term mortality risk and a clinical scale to predict the long-term risk of VPS placement.Neonates with IVH were identified from the Optum Clinformatics Data Mart administrative claims database. Matched maternal and childbirth characteristics were obtained for all patients. The primary endpoints of interest were short-term (30 day) mortality and long-term VPS placement. Classification of short-term mortality risk was evaluated using 5 different machine learning approaches and the best-performing method was validated using a withheld validation subset. Prediction of long-term shunt risk was performed using a multivariable Cox regression model with stepwise variable selection, which was subsequently converted to an easily applied integer risk scale.A total of 5926 neonates with IVH were identified. Most patients were born before 32 weeks' gestation (67.2%) and with low birth weight (81.2%). Empirical 30-day mortality risk was 10.9% across all IVH grades and highest among grade IV IVH (34.3%). Among the neonates who survived > 30 days, actuarial 12-month postdiagnosis risk of shunt placement was 5.4% across all IVH grades and 31.3% for grade IV IVH. The optimal short-term risk classifier was a random forest model achieving an area under the receiver operating characteristic curve of 0.882 with important predictors ranging from gestational age to diverse comorbid medical conditions. Selected features for long-term shunt risk stratification were IVH grade, respiratory distress syndrome, disseminated intravascular coagulation, and maternal preeclampsia or eclampsia. An integer risk scale, termed the Shunt Prediction After IVH in Neonates (SPAIN) scale, was developed from these 4 features, which, evaluated on withheld cases, demonstrated improved risk stratification compared with IVH grade alone (Harrell's concordance index 0.869 vs 0.852).In a large cohort of neonates with IVH, the authors developed a two-pronged, integrated, risk classification approach to anticipate short-term mortality and long-term shunt risk. The application of such approaches may improve the prognostication of outcomes and identification of higher-risk individuals who warrant careful surveillance and early intervention.

    View details for DOI 10.3171/2021.11.PEDS21390

    View details for PubMedID 35090135

  • An Analysis of Public Interest in Elective Neurosurgical Procedures during the COVID-19 Pandemic through Online Search Engine Trends. World neurosurgery Feng, A. Y., Garcia, C. A., Jin, M. C., Ho, A. L., Li, G. n., Grant, G. n., Ratliff, J. n., Skirboll, S. L. 2021


    In the wake of the COVID-19 pandemic, the Centers for Medicare & Medicaid Services (CMS) has recommended the temporary cessation of all elective surgeries. The effects on patients' interest of elective neurosurgical procedures are currently unexplored.Using Google Trends (GT), search terms of seven different neurosurgical procedure categories (Trauma, Spine, Tumor, Movement Disorder, Epilepsy, Endovascular, and Miscellaneous) were assessed in terms of relative search volume (RSV) between January 2015 and September 2020. Analyses of search terms were performed for over the short-term (Feb 18th, 2020-Apr 18th, 2020), intermediate-term (Jan 1st, 2020-May 31st, 2020) and long-term (Jan 2015-Sept 2020). State-level interest during phase I re-opening (Apr 28th, 2020-May 31st, 2020) was also evaluated.In the short-term, RSV of four categories (epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the intermediate-term, RSV of five categories (miscellaneous, epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the long-term, RSV of nearly all categories (endovascular, epilepsy, miscellaneous, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. Only the movement disorder procedure category had significantly higher RSV in states that reopened early.With the recommendation for cessation of elective surgeries, patient interest in overall elective neurosurgical procedures have dropped significantly. With gradual reopening, there has been a resurgence in some procedure types. GT has proven to be a useful tracker of patient interest and may be utilized by neurosurgical departments to facilitate outreach strategies.

    View details for DOI 10.1016/j.wneu.2020.12.143

    View details for PubMedID 33412316