tbuckley/cabot-search huggingface dataset:
RARE-05. ARE TRANSGENDER INDIVIDUALS STRONGLY PREDISPOSED TO DEVELOPMENT OF PROLACTINOMAS?
Authors: Bette Kleinschmidt-DeMasters
Journal: Neuro-Oncology (2019)

Abstract Transgender individuals usually receive long-term hormone treatment in the course of their sexual transition. Although the effects of this on possible development of neoplasia are largely unknown, very limited literature has suggested they may be predisposed to development of prolactinomas. We queried our databases to determine if we had encountered such cases at our tertiary care center for sellar region masses. Pathology databases from 2000–2019 were searched by the text word “transgender” to identify pituitary adenomas; cases were compared with all tissue specimens obtained from transgender persons. 2 pituitary adenomas were identified, out of approximately 1800+ sellar region masses at our institution during this same time period; neither were prolactinomas. The first occurred in a 71-year-old transgender male-to female who had undergone high-dose hormone therapy followed by orchiectomy 30 years prior; since that time various doses of estrogen had been received, most recently Premarin, .625 daily. Chronic hypertension associated with dizziness and vertigo prompted an endocrine workup which revealed an IGF-1 of 575 (normal &lt; 150 ng/ml). MRI disclosed a 10 X 7 X 13 mm. pituitary mass which proved to be a mixed somatotroph/ lactotroph adenoma. The second occurred in a 53-year-old transgender female-to-male who was being evaluated by an endocrinologist for hormone therapy for his transition when a slightly elevated prolactin level was discovered. MRI disclosed a 10 x 7 x 13 mm. pituitary mass. Transsphenoidal hypophysectomy showed a gonadotroph adenoma with patchy immunostaining for follicle stimulating hormone (FSH). In comparison, during this same time period, 60 other surgical specimens had been received, including 33 bilateral mastectomies, 15 hysterectomies, and 4 orchiectomies, almost all for gender transition purposes. Clinicians and pathologists may wish to be aware of the occurrence of pituitary adenomas in transgender individuals, although the incidence is quite low (2/1800 sellar region masses in our system).
Serum Metabolomic Profiling Correlated with ISS and Clinical Outcome for Multiple Myeloma Patients Treated with High Dose Melphalan and Autologous Stem Cell Transplantation
Authors: Ljupco Veskovski, Per-Ola Andersson, Ingemar Turesson, Daniel Malmodin, Anders Pedersen, Ulf-Henrik Mellqvist
Journal: Blood (2019)
Bromodomain and Extraterminal (BET) Domain Inhibition with PLX51107 and PLX2853 Improves Survival and Decreases Acute GVHD Severity in Murine Models
Authors: Hannah K. Choe, Yandi Gao, Katiri Snyder, Ben Powell, Gideon Bollag, Parvathi Ranganathan
Journal: Blood (2019)
A 14q32.31 Genomic-Imprinted DLK1-DIO3 microrna promotes Leukemogenesis By Inducing Stem Cell Quiescence and Inhibiting NK Cell Anti-Cancer Immunity
Authors: Giovannino Silvestri, Rossana Trotta, Lorenzo Stramucci, Shuzhen Wang, Ann-Kathrin Eisfeld, Bin Zhang, Klara Srutova, Gabriel Pineda, Catriona Jamieson, Fabio Stagno, Paolo Vigneri, Georgios Nteliopoulos, Martin Guimond, Peter Hokland, Michael W. Deininger, Francesco Dazzi, Dragana Milojkovic, Jane Apperley, Guido Marcucci, Xiaoxuan Fan, Maria R. Baer, Bruno Calabretta, Danilo Perrotti
Journal: Blood (2019)
Hypomethylating Agent and Venetoclax Combination Yields Comparable Outcomes to CPX-351 in Newly Diagnosed Acute Myeloid Leukemia
Authors: Hannah Asghari, Dasom Lee, Yehuda E. Deutsch, Onyee Chan, Najla Al Ali, Stephanie Boisclair, Constance Terrell, Eric Padron, Andrew T Kuykendall, Alan F. List, Hugo F. Fernandez, Jeffrey E. Lancet, David A Sallman, Rami S. Komrokji, Kendra L. Sweet, Chetasi Talati
Journal: Blood (2019)
TMIC-37. INTERCELLULAR COMMUNICATION BETWEEN NORMAL AND TUMOR CELLS IN GLIOMA MICROENVIRONMENT
Authors: Anwar Hossain, Irtiza Hasan, Satoshi Adachi, Daniel Ledbetter, Malcolm McDonald, Joy Gumin, Marc Daou, Lynette Phillips, Brittany Parker-Kerrigan, Frederick Lang
Journal: Neuro-Oncology (2019)

Abstract The interactions between tumors cells and their microenvironment are increasingly recognized as contributors to tumor growth and therapeutic resistance in glioblastoma (GBM). Mesenchymal Stem Cells (MSCs) have been implicated as components of the microenvironment of several cancers, but their contribution to GBM remains obscure. Recently we reported that GBMs contain cells resembling human mesenchymal stem cells, called Glioma-associated-MSCs (GA-hMSCs), based on our ability to isolate these cells from patient tumors (Figueroa, et al. Can Res 2017. 77, 5808–5819). In order to characterize the function of these cells in vivo, we used a PDGFRb promoter driven mouse model to track and modulate the behavior of endogenous MSCs (PDGFRb + cells). To generate tumors that mimic gliomas, we injected the RCAS-PDGF avian retrovirus into PDGFRb EGFP/nTVA mice. These mice express EGFP in PDGFRb expressing cells and RCAS receptor TVA under the control of the Nestin promoter and develop tumors. Immunostaining these tumors for GFP and CD31 determined that MSC like cells reside around blood vessels and are likely the major contributor of microvascular proliferation often seen in human gliomas. Additionally, we sought to see if there was communication between MSCs localized around blood vessels and the tumor. To this end, mice with Cre recombinase expression under the PDGFRb promoter were implanted with a GL-261 tumor harboring a dsRed/eGFP Cre recombinase/LoxP site. In these mice, tumor color change from red to green indicates transfer of Cre mRNA or protein from PDGFRb+ cells (MSCs) to tumor cells (GL-261dsRed/eGFP). We observed red to green transition in tumors, indicating that there is transfer of mRNA or protein, and further suggesting that there is direct communication between the tumor microenvironment and the tumor. Taken together, our findings emphasize the crucial role of MSCs in the tumor microenvironment.
NIMG-59. ADVERSE EFFECTS OF IMAGE TILING FOR AUTOMATIC DEEP LEARNING GLIOMA SEGMENTATION IN MRI
Authors: G Anthony Reina, Siddhesh Thakur, Ravi Panchumarthy, Spyridon Bakas
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Application of deep learning to neuro-oncology has shown promising clinically relevant results for tumor classification, localization, and segmentation. Hardware limitations, typically memory size of graphics cards, prevent magnetic resonance imaging (MRI) volumes from being processed as a whole, and hence they are divided into smaller, overlapping tiles. Deep learning algorithms (e.g., U-Net) can then be trained and applied for predictions on such tiles, followed by their combination/stitching as the final prediction for the whole volume. We investigate the hypothesis that image tiling options, such as tile placing, size, overlap, and stitching, introduce variations with adverse effects on predictions, both in terms of inconsistency and accuracy. METHODS We utilized the publicly available BraTS 2018 dataset of 285 baseline pre-operative MRI glioma scans, with corresponding expert tumor boundary annotations. We implemented a 3D U-Net to predict boundaries of the whole tumor extent, by virtue of the abnormal hyper-intense signal of T2-FLAIR scans. RESULTS Simply flipping the tile horizontally, or translating it by one voxel, produces different predictions. Use of small tiles (64x64x64 voxels) yields substantially more false positive predictions than when using larger tile size (i.e., 128x128x128 voxels). Overlapping tiles produce conflicting predictions, leading to ambiguous interpretations upon their stitching. In areas of overlapping tiles, rounding followed by averaging the overlapping predictions produce superior results to the inverse sequence. All these are particularly noticeable in the margins of the abnormal signal and in areas of large contrast variation. CONCLUSIONS Although tiling is a workaround for hardware limitations, it introduces variations detrimental to accuracy. Tiling of neuro-oncology scans for computational analysis using deep learning leads to non-generalizable, non-reproducible results, thereby affecting the performance and potential clinical translatability of such algorithms. Careful considerations and standardization recommendations should be established and appropriately documented for performing such analyses, in order to avoid misinterpretation of results.
Pyelonephritis in Pregnancy
Authors: H RUF
Journal: BMJ (1962)

BiuTuB 1069 in figures for the latter was probably related to improved diabetic control in pregnancy.During pregnancy insulin requirements might rise, particularly from the 28th week onwards, but pregnancy was not diabetogenic.However, delivery by caesarean section or induced labour was usually advisable between the 36th and 38th week. Pyelonephritis
Outcomes of Patients with Refractory Peripheral T-Cell Lymphoma, Angioimmunoblastic and Other Nodal Lymphomas of T Follicular Helper-Cell Origin (OPerA)
Authors: Joanna M Rhodes, Suchitra Sundaram, Adam Zayac, Adam J Olszewski, Paolo Caimi, Zachary Braunstein, Jonathan E Brammer, Waqas Jehangir, Elvira Umyarova, Sheenu Sheela, Nilanjan Ghosh, Sunita Dwivedy Nasta, Stefan K. Barta
Journal: Blood (2019)
Ventilator-associated pneumonia due to Stenotrophomonas maltophilia: Risk factors and outcome
Authors: Wafa Ibn Saied, Sybille Merceron, Carole Schwebel, Alban Le Monnier, Johana Oziel, Maité Garrouste-Orgeas, Guillaume Marcotte, Stéphane Ruckly, Bertrand Souweine, Michael Darmon, Lila Bouadma, Etienne de Montmollin, Bruno Mourvillier, Jean Reignier, Laurent Papazian, Shidasp Siami, Elie Azoulay, Jean-Pierre Bédos, Jean-Francois Timsit
Journal: Journal of Infection (2019)
Nonmyeloablative Allogeneic Transplantation (NMAT) Confers an Overall Survival Benefit with Similar Non-Relapse Mortality When Compared to Autologous Stem Transplantation (ASCT) for Patients (pts) with Relapsed Follicular Lymphoma (FL)
Authors: Issa F. Khouri, Denái R. Milton, Celina Ledesma, Loretta J. Nastoupil, Elias Jabbour, Paolo Anderlini, Qaiser Bashir, Stefan O. Ciurea, May Daher, Luis E. Fayad, Jin S Im, Swaminathan P. Iyer, David Marin, Rohtesh S. Mehta, Jeffrey J. Molldrem, Amanda L. Olson, Betul Oran, Uday Popat, Muzaffar Qazilbash, Samer Srour, Felipe Samaniego, Gabriela Rondon, L. Jeffrey Medeiros, Alison Gulbis, Richard E Champlin
Journal: Blood (2019)
Abstract 17145: Outcomes of Transcatheter Occlusion of Patent Ductus Ateriouses in Infants ≤ 6 Mouths
Authors: Yimin Hua, Yifei Li, Kaiyu Zhou
Journal: Circulation (2018)

Objectives: We sought to analyze the outcomes of transcatheter patent ductus arteriosus (PDA) occlusion using a variety of devices in infants ≤ 6 mouths and discuss the transcatheter occlusion indication of PDA in early infants. Methods and Results: A total of 72 patients underwent successful transcatheter device closure. The mean age at catheterization was 4.9±1.8months (1-6 months) with a mean weight at catheterization of 5.1±1.9kg (1.9-6.7kg), the mean PDA diameter of 3.9±0.8mm (1.8-5.3mm),the mean systolic pulmonary arteriosus pressure of 55.7±8.9 mmHg (46-79mmHg). Among these suffered infants, companied with 72cases of growth retardation, 48 cases of recurrent lower respiratory tract infection, 35 cases associated with congestive heart failure, and 5 cases of respirator-oxygen-dependent. 4/6-8/10 PDA occluder was selected for transcatheter device closure, and intraoperative blood transfusion were performed in 46 cases. All subjects resulted with occluder position in good shape, no residual shunt; whileas 16 cases with aortic blood flow velocity increased slightly, 12 cases with left pulmonary artery blood flow velocity increased slightly just postoperation. And in follow-ups the increased velocity of and pulmonary blood flow gradually returned to normal. Follow-up data showed, all subjects resulted good outcomes with growth significantly improved, congestive heart failure cured and repeated lower respiratory tract infection significantly reduced postoperative. Conclusions: In experienced heart center, percutaneous closure of PDA should be considered even in infants ≤ 6 mouths. The indications include PDA infants with respirator-oxygen-dependent, congestive heart failure, and recurrent lower respiratory tract infection and growth retardation. Children underwent PDA occlusion would result with improved growth and development, recovered heart function and less lower respiratory tract infection.
The Role of the Lipid Raft-Associated Protein Flotillin-2 during Development and Progression of Myeloid Leukaemia
Authors: Rahul Kumar, Raquel Pereira, Julian Niemann, Costanza Zanetti, Alex Azimpour, Melanie Meister, Parimala Sonika Godavarthy, Daniela S. Krause
Journal: Blood (2019)
Association of Epstein-Barr Virus Reactivation with the Recovery of CD4/CD8 Double Negative T Lymphocytes after Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Zhilei Bian, Jiangying Liu, Lan-Ping Xu, Ying-Jun Chang, Yu Wang, Xiao-Hui Zhang, Xiao-Jun Huang
Journal: Blood (2016)
MNGI-13. DYNAMIC IMAGING OF MENINGIOMA WITH 3’-DEOXY-3’-[18F]-FLUOROTHYMIDINE USING POSITRON EMISSION TOMOGRAPHY: A POSSIBLE PREDICTOR OF TUMOR GROWTH
Authors: Asma Bashir, Mark Bitsch Vestergaard, Lisbeth Marner, Vibeke A Larsen, Morten Ziebell, Kåre Fugleholm, Ian Law
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Positron emission tomography (PET) with 3’-deoxy-3’-[18F]-fluorothymidine (18F-FLT) provides a non-invasive assessment of in vivo tumor proliferation that could be useful for predicting growth potential in meningiomas. We aimed to study static and dynamic 18F-FLT PET metrics prospectively to assess metabolic activity of meningioma, and their associations to potential tumor growth on subsequent MRI scans. METHODS Between April 2017 and December 2018, 44 patients harboring MRI-suspected (n = 37) and histologically-verified residual meningiomas (n = 7) underwent a 60-minute dynamic 18F-FLT PET prior to imaging surveillance. Maximum and mean standardized uptake values (SUVmax, SUVmean) with/without normalisation to blood radioactivity obtained from a 40-60-minute static PET image and a 60-minute venous blood sampling were calculated. Total volume of distribution (VT) was estimated by kinetic modeling using a two-tissue reversible compartmental model with a fractional blood volume and metabolite-corrected image-derived input function. Tumor growth rate was calculated by volumetric analysis of subsequent MRI scans. RESULTS At the time of this writing, a total of 53 follow-up MRI scans from 33 patients were available for review, with a median follow-up time of 11 months (range, 4–22.5 months). Tumor growth/progression was observed in 12 cases with a monthly median growth rate of 0.10 cm3 (range, 0.03–3.41 cm3). All 18F-FLT metrics were significantly higher in patients with radiological progression compared to patients with stable findings with maximum tumor-to-blood-ratio (TBRmax) as the most promising imaging biomarker (4.9 ± 1.4 vs. 3.4 ± 1.0, P = .003; Mann-Whitney) and the strongest predictor for tumor progression (hazard ratio, 3.125; 95% confidence interval, 1.390–7.028; P = .006; univariate binary logistic regression). Age, gender, previous residual remnant(s) and initial tumor volume (median, 3.1 cm3; range, 0.2–55.3 cm3) had no influence. CONCLUSION 18F-FLT PET imaging could be a valuable tool in designing a patient-tailored surveillance strategy for patients with asymptomatic meningiomas.
ATM activity in T cells is critical for immune surveillance of lymphoma in vivo
Authors: Arina Riabinska, Daria Lehrmann, Ron Daniel Jachimowicz, Gero Knittel, Christian Fritz, Anna Schmitt, Aenne Geyer, Carola Heneweer, Maike Wittersheim, Lukas P. Frenzel, Alessandro Torgovnick, Janica Lea Wiederstein, Claudia Maria Wunderlich, Monika Ortmann, Arlette Paillard, Wilhelm Wößmann, Arndt Borkhardt, Stefan Burdach, Martin-Leo Hansmann, Andreas Rosenwald, Sven Perner, Gita Mall, Wolfram Klapper, Andrea Merseburg, Marcus Krüger, Holger Grüll, Thorsten Persigehl, Frank Thomas Wunderlich, Martin Peifer, Olaf Utermöhlen, Reinhard Büttner, Filippo Beleggia, Hans Christian Reinhardt
Journal: Leukemia (2019)
CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma
Authors: Bryan D. Choi, Xiaoling Yu, Ana P. Castano, Henia Darr, Daniel B. Henderson, Amanda A. Bouffard, Rebecca C. Larson, Irene Scarfò, Stefanie R. Bailey, Genevieve M. Gerhard, Matthew J. Frigault, Mark B. Leick, Andrea Schmidts, Jason G. Sagert, William T. Curry, Bob S. Carter, Marcela V. Maus
Journal: Journal for ImmunoTherapy of Cancer (2019)

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas and other cancers can hamper CAR T cells is through surface expression of inhibitory ligands such as programmed cell death ligand 1 (PD-L1). Using the CRIPSR-Cas9 system, we created universal CAR T cells resistant to PD-1 inhibition through multiplexed gene disruption of endogenous T-cell receptor (<i>TRAC</i>), beta-2 microglobulin (<i>B2M</i>) and PD-1 (<i>PDCD1</i>). Triple gene-edited CAR T cells demonstrated enhanced activity in preclinical glioma models. Prolonged survival in mice bearing intracranial tumors was achieved after intracerebral, but not intravenous administration. CRISPR-Cas9 gene-editing not only provides a potential source of allogeneic, universal donor cells, but also enables simultaneous disruption of checkpoint signaling that otherwise impedes maximal antitumor functionality.
Daratumumab in Patients with Multiple Myeloma and Renal Impairment - Real-World Data from a Single-Center Institution
Authors: Jorge Monge, Robin S. Solomon, Kari Flicker, David S Jayabalan, Jin Guo, Jorge Contreras, Kathleen Pogonowski, Natalie Agudo, Danielle Guarneri, Brielle Liotta, Eloisi Caldas Lopes, Roger Pearse, Morton Coleman, Ruben Niesvizky, Adriana C. Rossi
Journal: Blood (2019)
Clinical Outcome of an Multicentre, Randomized, Phase II Clinical Trial for Patients with Extranodal NK/T Cell Lymphoma Treated By P-Gemox or Aspametdex
Authors: Hui-qiang Huang, Gao Yan, Hang Su, Yunhong Huang, Yuhuan Gao, Wang Xiaoxiao, Bai Bing, Yujing Zhang, Liping Su, Xiaoxia Chu, Wenyu Li, Junyi Zhang, Qiaohua Zhang, Liansheng Zhang, Xiaohua Hu, Liqun Zou, Zhiming Li, Wenqi Jiang
Journal: Blood (2019)
IMMU-46. EXAMINATION OF THE EFFECTS OF DEXAMETHASONE ON THE EFFICACY OF IMMUNOTHERAPY IN GLIOMA USING GENE-MEDIATED CYTOTOXIC IMMUNOTHERAPY
Authors: Marilin Koch, Mykola Zdioruk, M Oskar Nowicki, Estuardo Aguilar, Laura Aguilar, Brian Guzik, Ennio Chiocca, Sean Lawler
Journal: Neuro-Oncology (2019)

Abstract RATIONALE Dexamethasone is frequently used in symptomatic treatment of glioma patients, although it is known to cause immune suppression. Checkpoint inhibitor immunotherapies have not yet been successful in glioma treatments. Gene-mediated cytotoxic immunotherapy (GMCI) is an immunotherapeutic approach that uses aglatimagene besadenovec with an anti-herpetic prodrug to induce immunogenic tumor cell death and immune cell attraction to the tumor site with potent CD8 T cell activation. GMCI is currently in clinical trials for solid tumors including glioblastoma, where it showed encouraging survival results in a Phase 2 study that did not limit the use of dexamethasone. However, the effects of dexamethasone on its efficacy have not been explored. METHODS We investigated the effects of dexamethasone on GMCI in vitro using cytotoxicity and T-cell-killing assays in glioblastoma cell lines. The impact of dexamethasone in vivo was assessed in an orthotopic syngeneic murine glioblastoma model. RESULTS Cyotoxicity assays showed that Dexamethasone has a slight impact on GMCI in vitro. In contrast, we observed a highly significant effect in T-cell-functional assays in which killing was greatly impaired. Immune cell response assays revealed a reduced T-cell proliferation after co-culture with supernatant from dexamethasone or combination treated glioblastoma cells in contrast to GMCI alone. In a murine model, the combination of GMCI and dexamethasone resulted in a significant reduction in median symptom-free survival (29d) in comparison to GMCI alone (39.5d) (P = 0.0184). CONCLUSION Our data suggest that high doses of dexamethasone may negatively impact the efficacy of immunotherapy for glioma, which may be a consequence of impaired T cell function. These results support the idea that there is a need in identifying possible alternatives to dexamethasone to maximize the effectiveness of immunostimulatory therapies such as GMCI.
Abstract 15817: Immediate versus Deferred Revascularization in NSTEMI
Authors: Micaela Iantorno, William S Weintraub, Rebecca Torguson, Deepakraj Gajanana, Zou Quan, Itsik Ben-dor, Hector M Garcia-garcia, Lowell Satler, Toby Rogers, Ron Waksman
Journal: Circulation (2018)

Introduction: It is estimated that in the United States, each year, >780,000 persons will experience an acute coronary syndrome (ACS). Approximately 70% of these will have non ST elevation-myocardi...
Response to Letters Regarding Article, “Differential Impact of Blood Pressure-Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study”
Authors: Bryan Williams, Peter S. Lacy, Herbert Thurston, Simon Thom, Alun Hughes, Kennedy Cruickshank, Alice Stanton, David Collier, Michael O’Rourke
Journal: Circulation (2006)
EXTH-19. IBRUTINIB MODULATES BLOOD-BRAIN BARRIER INTEGRITY TO ENHANCE CHEMOTHERAPY PERMEABILITY
Authors: Caitlin Meeks, Amelie Vezina, Robert Robey, Michael Gottesman, Sadhana Jackson
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The blood-brain barrier (BBB) poses a major treatment challenge for malignant brain tumors. Ibrutinib is an FDA approved Bruton’s tyrosine kinase (BTK) and bone marrow x-linked tyrosine kinase (BMX) inhibitor indicated for the treatment of B-cell lymphomas. BMX is highly expressed in endothelial cells and is suggested to regulate cytoskeletal organization and barrier function in epithelial cells. We hypothesize that inhibition of BMX by ibrutinib in brain endothelial cells will disrupt the integrity of the BBB to increase drug permeability. METHODS Protein expression and phosphorylation of BMX was confirmed in immortalized mouse brain endothelial cells (bEnd.3). Endothelial barrier integrity was evaluated with increasing doses of ibrutinib (1–30μM) for 24hrs via the ACEA xCELLigence system (impedance) and the ECIS TEER24 system (resistance). Paracellular permeability of doxorubicin was measured by fluorescent spectrophotometry. Junctional protein expression of VE-Cadherin and F-actin cytoskeletal organization were detected by fluorescent staining. Ibrutinib’s effect on efflux pumps, ABCB1 and ABCG2, was performed by flow cytometry using specific substrates, valspodar and FTC, respectively. RESULTS Ibrutinib decreased endothelial cell impedance in a dose-dependent manner over 24hrs, with transient decrease by 46% at 30min with an optimal dose of 1μM, and partial recovery by 4hrs. TEER was decreased by 60% at 3hrs. Ibrutinib enhanced doxorubicin permeability by 30%; attributed to the transient disorganized nature of actin cytoskeletal filaments 2hrs post treatment. No effects on VE-cadherin expression or localization were observed. Ibrutinib successfully inhibited activity of ABCB1 and ABCG2 in a dose-dependent manner. CONCLUSION Our results suggest ibrutinib causes transient disruption of the brain endothelial monolayer due to cytoskeletal disorganization and ABC transporter inhibition to enhance permeability of doxorubicin. Further studies using ibrutinib and cytotoxic agents are warranted in glioma bearing animals. We propose that using ibrutinib as an adjunctive therapy may enhance drug delivery to patients with malignant brain tumors.