tbuckley/cabot-search huggingface dataset:
ATIM-16. MRI-GUIDED CONVECTIVE DELIVERY OF MDNA55, AN INTERLEUKIN-4 RECEPTOR TARGETED IMMUNOTHERAPY FOR THE TREATMENT OF RECURRENT GLIOBLASTOMA
Authors: Krystof Bankiewicz, Achal Achrol, Manish Aghi, Martin Bexon, Andrew Brenner, Nicholas Butowski, Bradley Elder, John Floyd, Russell Lonser, Fahar Merchant, Merchant Rosemina, Toral R Patel, Dina Randazzo, Mark Souweidane, Michael Vogelbaum, Frank D Vrionis, John Sampson
Journal: Neuro-Oncology (2017)

Intratumoral glioblastoma therapy has been limited by suboptimal spatial distribution of therapeutic agents. MR-guided convection-enhanced delivery (CED) of MDNA-55 (interleukin-4 fused to Pseudomonasexotoxin) is underway in a Phase 2 open-label study in up to 43 patients with recurrent glioblastoma. Gadolinium-based contrast agent (Gd-DTPA) is co-infused with MDN55 to optimize intra-tumoral catheter placement, monitor drug distribution and identify non-functional catheters. MR images acquired prior to, during, and following infusion are used to determine drug distribution, tissue response, and disease status. Depending on the tumor size up to 60 mL of MDNA55 at a concentration of 1.5 μg/mL is administered as a single infusion through each catheter for a maximum dose of 90 μg. We report preliminary results of tumor distribution in 6 subjects that underwent MR-guided delivery of MDNA55 via implantable flexible catheters. Target enhancing tumor volume varied between 1.5 to 24 mL and tumor diameter varied between 1.8 to 4.7cm. Volume of infusion ranged between 14 to 66 mL and was delivered via 1 to 3 catheters at a flow rate of up to 15mL/min per catheter. MR was employed to monitor initial infusion, allowing adjustment of catheter depth as needed. The bulk of the delivery was performed outside the MR scanner in awake patients. MR confirmation of the distribution was performed within 4 hours post-infusion. In all patients, remarkable tumoral and peri-tumoral distribution has been observed. Tumor coverage ranged from 43% to 100%. Ratio of volume of distribution (Vd) to the volume infusion (Vi) ranged from 2.2 to 0.6. Lower Vd/Vi ratios were associated with drug leakage into the CSF space and/or resection cavity. When catheter placement was inaccurate, real-time imaging of Gd-DTPA distribution enabled adjustments to catheter depth which dramatically improved tumor coverage. MR-guidance during CED is therefore critical for optimal drug distribution in brain tumors.
NIMG-54. NEURONAL CORRELATES OF COGNITIVE FUNCTION IN PATIENTS WITH CHILDHOOD CEREBELLAR TUMOR LESIONS
Authors: Christian Dorfer, Johanna Reichert, Monika Chocholous, Ulrike Leiss, Thomas Pletschko, Gregor Kasprian, Julia Furtner, Kathrin Kollndorfer, Daniela Prayer, Thomas Czech, Irene Slavc, Veronika Schöpf
Journal: Neuro-Oncology (2017)

While it has been shown that treatment for cerebellar tumors has an impact on cognitive functions, the extent to which they shape distant neuronal pathways is still largely undescribed. Thus, the present neuroimaging study investigated different aspects of cognitive function and their neuronal correlates in patients after childhood cerebellar tumor surgery. Three different tasks (an alertness task, a working memory task and an incompatibility task) were performed by 11 patients after childhood cerebellar tumor surgery and 17 healthy controls. Neuronal correlates as reflected by alterations in functional networks during tasks were assessed by means of group independent component analysis. We were able to identify eight networks involved during task performance: Default mode network, precuneus, anterior salience network, executive control network, visual network, auditory and sensorimotor network and a cerebellar network. For the most ‘basic’ cognitive tasks, a weaker task-modulation of default mode network, left executive control network and the cerebellar network was observed in patients compared to controls. Results for higher-order tasks are in line with a partial restoration of networks responsible for higher-order task execution. Our results provide tentative evidence that the synchronicity of brain activity in patients was at least partially restored through neuroplastic reorganization, particularly for networks related to higher-order cognitive processes. The complex activation patterns underline the importance of testing several cognitive functions to assess the specificity of cognitive deficits and neuronal reorganization processes after brain lesions.
P1.02-044 Relationship between RET Rearrangement and Thymidylate Synthase mRNA Expression in Non-Small Cell Lung Cancer Tissues
Authors: C. Xu, W. Wang, W. Zhuang, Z. Song, G. Chen, Y. Tian, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
PALL-04. EVALUATION OF PROACTIVE AND RESCUE ENTERAL TUBE FEEDINGS IN CHILDREN UNDERGOING TREATMENT FOR MEDULLOBLASTOMA AND SUPRATENTORIAL PNET, A SINGLE INSTITUTION RETROSPECTIVE CHART REVIEW
Authors: Anne Bendel, Rachel Laquere, Katherine Ingram, Amy Linabery, Amanda Nickel, Melissa Hansen, Julie Pape-Blabolil, Mary Skrypek, Charles Bendelsmith
Journal: Neuro-Oncology (2017)

Medulloblastoma and supratentorial primitive neuroectodermal tumors (sPNET) require aggressive treatment to ensure the best chance of cure. Malnutrition, a common treatment complication, is associated with increased morbidity. Children’s Minnesota initiated proactive enteral tube feedings (ETF) in patients undergoing treatment for medulloblastoma/sPNET in 2005 for infants (<3 years) and in 2011 for children (≥3 years) with the goal of maintaining weight throughout treatment. We conducted a retrospective chart review of patients aged 0-19 years treated for newly diagnosed medulloblastoma and sPNET in 2002-2017 to assess changes in relative weight associated with ETF. Patients were categorized as receiving proactive ETF (initiated within 1 month of diagnosis; n=33), rescue ETF (initiated >1 month after diagnosis in response to weight loss; n=7), or no ETF (n=23). We evaluated differences in mean relative weights (weight-for-height Z-scores) from diagnosis to last chemotherapy cycle, overall and across ETF subgroups, performing t-tests and F-tests, respectively. Relative weights decreased over the course of treatment in all patients combined with a mean difference in Z-scores (SD)= -0.34 (0.86); p=0.003. In examining ETF treatment groups separately, those receiving proactive ETF (-0.09 (0.88)) showed significantly less decline in relative weight compared to those receiving no ETF (-0.66 (0.84); p=0.04); mean change in relative weights of those receiving rescue ETF was indistinguishable from the other groups (p>0.05). Visual inspection of local regression curves confirmed that Z-score trajectories for the proactive and no ETF groups differed, where the proactive group maintained their relative weight further into treatment before declining. Conclusions: In this interim analysis, children and adolescents who received proactive ETF experienced negligible changes in relative weight during treatment, while those who received no ETF experienced substantial decline. Our results suggest that proactive ETF is effective at maintaining weight over the course of treatment for pediatric medulloblastoma and sPNET.
EXTH-48. THE KETONE BODY β-HYDROXYBUTYRATE CHEMO- AND RADIO-SENSITIZES MALIGNANT GLIOMA CELLS BY INHIBITING HISTONE DEACETYLASE ACTIVITY AND DOWNREGULATING EXPRESSION OF RAD51
Authors: Eric C Woolf, Aditi Bhattacharya, Alex P Rossi, Makena M Davidson, Nelofer Syed, Adrienne C Scheck
Journal: Neuro-Oncology (2017)

Mounting evidence suggests that raising blood ketones and reducing blood glucose may be an effect anti-glioma strategy. We have demonstrated that this approach not only impacts multiple hubs of glioma growth but also greatly increases survival in a mouse model of malignant glioma when administered in combination with temozolomide or radiation. However, the underlying mechanisms have not been fully elucidated. To examine these mechanisms we explored the anti-tumor properties of the ketone body β-hydroxybutyrate (BHB). We demonstrated that BHB treatment alone radiosensitizes mouse glioma, human glioblastoma and human glioma stem-like cells in vitro. Furthermore, BHB resensitized resistant cells to radiation and TMZ. We also showed that BHB inhibits the activity of histone deacetylases (HDACs) and increases the expression of microRNAs that regulate DNA repair genes. Evidence suggests that HDAC inhibition can impact DNA damage repair in cancer cells. We therefore assessed the impact of BHB on DNA damage repair pathways. In mouse malignant glioma cells BHB treatment lead to decreased expression of proteins involved in DNA repair and increased radiation-induced expression of the double stranded DNA break marker γ-H2AX. Specifically, BHB treatment led to decreased expression of RAD51, a crucial regulator of homologous repair. This was validated in mouse malignant glioma cells and several human glioblastoma (GBM) cell lines. RAD51 expression has also been linked to temozolomide (TMZ) resistance. We therefore tested the impact of BHB on response to TMZ in vitro. BHB sensitized human GBM cells to TMZ¸ possibly through modulation of O6-methylguanine DNA methyltransferase (MGMT) expression. As clinical interest in ketogenic therapies and exogenous ketone supplementation increases it is paramount that the precise mechanisms underlying this approach are elucidated, particularly as they impact standard of care. These data shed light on these mechanisms and bring us closer to understanding how to best implement it for clinical use.
P1.06-014 Higher Body Mass Index Prolongs Survival Time in Non-Small Cell Lung Cancer with Good Performance Status
Authors: T. Suzumura, T. Kawaguchi, S. Mitsuoka, T. Kimura, N. Yoshimura, N. Yoshimoto, K. Sawa, Y. Matsumoto, K. Hirata
Journal: Journal of Thoracic Oncology (2017)
Guías BICHAT para el manejo clínico del muermo y de la melioidosis y del muermo y de la melioidosis relacionados con el bioterrorismo
Authors: P Bossi, A Tegnell, A Baka, F van Loock, J Hendriks, A Werner, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

El muermo y la melioidosis, o pseudomuermo, son dos enfermedades infecciosas debidas a Burkholderia mallei y Burkholderia pseudomallei respectivamente. La infeccion puede adquirirse por contacto directo de la piel con tierra o agua contaminada. La ingestion de agua o polvo contaminado es otra forma de contaminacion. El muermo y la melioidosis ya fueron estudiadas en varios paises como armas biologicas en potencia. Producen sindromes clinicos similares. Los sintomas dependen de la via de infeccion, pero una forma de la enfermedad puede llevar a otra, o el curso de la enfermedad puede transformarse en recurrente cronico. Se han descrito cuatro formas clinicas generales: infeccion localizada, infeccion pulmonar, septicemia e infecciones supurativas cronicas de la piel. Todos los tratamientos recomendados deben adaptarse a la susceptibilidad de cualquiera de los aislamientos obtenidos. Se recomienda profilaxis posterior a la exposicion con trimetoprim-sulfametoxazol en caso de ataque biologico. No hay vacuna para el hombre.
Evidence Supports Action to Prevent Injurious Falls in Older Adults
Authors: Eric B. Larson
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
SCDT-49. VALUE OF T2-WEIGHTED MR IMAGING TO EVALUATE DRUG DISTRIBUTION THE BRAIN STEM OF CHILDREN
Authors: E Wembacher-Schroeder, Z Zhou, N Pandit-Tasker, MM Souweidane
Journal: Neuro-Oncology (2017)

In the context of a Phase I clinical trial for pediatric DIPG we used MRI guided convection-enhanced delivery (CED) to administer a radio immunotherapy drug. After preliminary trajectory planning the MRI guided stereotactic procedures were performed using a MR-compatible skull mounted guidance device (ClearPoint®). A flexible step-design infusion catheter (Brainlab Flexible Catheter) was used for administration of infusion in a monitored setting over several hours. MR and PET scanning were employed after completion of infusion for distribution assessment. In this study we evaluated the value of T2-weighted MR as a measure of distribution volume. For analysis, data collected for the subjects in the latter cohorts were used to determine infusate distribution, defined as hyperintense signal change on post-infusion T2-weighted images compared to pre-infusion T2-weighted images. The signal increase was outlined using a semi-automatic threshold segmentation technique (iPlan® Flow) and visually compared to the distribution of the radio labeled drug visualized with positron emission tomography (PET). On visual assessment, an increase in signal intensity on post infusion T2-weighted images was seen in all subjects analyzed. In patients with minimal or no pre-infusion signal abnormality on T2-weighted images, the geometry of change in T2 signal intensity closely matched the geometry of the activity measured via PET. In cases with intense pre-existing hyperintense T2 signal, T2-weighted images underestimated the distribution compared to PET. Hyperintense signal changes depicted on T2-weighted imaging following CED provides useful information on CED distribution and qualitatively correlates with the geometry of the radio immunotherapy drug distribution on PET. Application of this method provides a feasible alternative for future pediatric brainstem trials without a theragnostic agent or gadolinium co-infusion.
The Lost Art of Doctoring
Authors: Sarah M. Mitchell
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
TMIC-24. ASTROCYTE-DEPENDENT ENHANCEMENT OF GLIOBLASTOMA GROWTH AS A CANDIDATE THERAPEUTIC TARGET
Authors: Alessandro Mega, Mette Hartmark Nilsen, Lina Wik Leiss, Linda Sleire, Jianping Liu, Sven Nelander, Lene Uhrbom, Cecilia Krona, Daniel Hägerstrand, Per Øyvind Enger, Monica Nistér, Arne Östman
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme is a deadly disease with a need for deeper understanding and new therapeutic approaches. The tumor microenvironment is part and parcel of cancer biology. The astrocytes and other cell types of the tumor microenvironment of glioblastoma have been suggested to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through in vitro approaches and in an in vivo model. Our results show that the astrocytes enhance glioblastoma cell growth in commercially available cell lines and a primary culture. Furthermore, orthotopic co-injection of astrocytes and glioblastoma cells reduces survival in NOD/scid mice compared to glioblastoma cell mono-injection. Gene expression profiling revealed about 400 genes in the astrocytes that are regulated by co-culture with glioblastoma cells. A high-throughput screening has been designed to identify drugs capable of interfering with the GBM-HA crosstalk. Out of 1200 compounds, 12 have been validated as specifically acting on GBM growth in co-culture. Two of them have been selected for further studies, having shown reproducibility on other GBM cultures. In conclusion, this study suggests that astrocytes contribute to growth of glioblastoma and imply this crosstalk as a candidate target for novel therapies.
EXTH-19. COMBINATION OF IN VITRO TUMOR TREATING FIELDS AND TEMOZOLOMIDE DECREASE PROLIFERATION IN PATIENT-DERIVED GLIOBLASTOMA CELL LINES
Authors: Sharon K Michelhaugh, Sam Kiousis, Sandeep Mittal
Journal: Neuro-Oncology (2017)

Tumor treating fields (TTFields) are FDA-approved for treatment of newly-diagnosed and recurrent glioblastoma. Adding TTFields therapy to standard-of-care temozolomide (TMZ) extended progression-free survival and overall survival in newly-diagnosed glioblastoma patients. In this study, cell lines generated from newly-diagnosed glioblastoma patients were treated in vitro with TTFields ± TMZ followed by proliferation assays. Single-cell suspensions generated from tumor tissues obtained from newly-diagnosed patients (n=3) were cultured in DMEM/F12 media with 10% fetal bovine serum and gentamicin. Prior to TTFields initiation, cells were plated on plastic coverslips (1 × 104cells/coverslip; n=4–6/group) and incubated overnight. Then, TTFields were applied at 200 kHz with a field intensity of ~1.6 V/cm for 12–14 days. Cells were treated with TTFields with or without 50 µM TMZ for 5 days. After 5 days, proliferation was assessed with XTT assay and TTFields resumed without TMZ for another 7 days followed by a second XTT assay. XTT data were analyzed by t-test or one-way ANOVA with Tukey’s post-hoc test. In patient-derived glioblastoma cells treated with TTFields for 14 days, proliferation was 41.1–41.6% control (p<0.0001). In TMZ combination experiments, after 5 days of TMZ, TTFields, or both, proliferation was 69.9% control, 53.9% control, and 29.2% control, respectively (p<0.0001). Following an additional 7 days of TTFields treatment (after TMZ washout), the TMZ group was unchanged at 68.8% control, while in TTFields treated cells, proliferation further decreased to 37.6% control with the combination reducing proliferation down to 11.6% control (p<0.01). In patient-derived glioblastoma cell lines generated from newly-diagnosed patients, concurrent TTFields with a regimen that mimics TMZ maintenance therapy produced a ~90% reduction in proliferation and was a significantly greater reduction than in either single treatment group, supporting combination therapy with TMZ and TTFields for glioblastoma patients.
EXTH-71. HYPERPOLARIZED [1-13C] PYRUVATE AS A BIOMARKER FOR TREATMENT MONITORING IN LYMPHOMA MURINE MODELS
Authors: Brice Tiret, Adam Autry, Ilwoo Park, Ming Lu, Rana Anjum, Liza Drew, Sebastien Degorce, Michele Mayo, Keith Dillman, James Rubenstein, Myriam M Chaumeil
Journal: Neuro-Oncology (2017)

In primary central nervous system lymphoma (PCNSL), L265P mutation of the myeloid differentiation 88 (MYD88) protein is the most common, and induces a constitutive activation of IRAK4 kinase, IRAK1 phosphorylation and increased NF-kB signaling, offering a unique window for therapeutic development. We previously show that AZ1495, a potent inhibitor of IRAK4, significantly delayed progression and improved OS in L265P-mutated PCNSL models [ASH 2016], highlighting the clinical potential of IRAK inhibition. In the clinic however, early monitoring of such targeted therapies remains challenging using conventional imaging, as treatment often results in non-readily detectable anatomical changes. Here, we questioned the potential of a new neuroimaging method, hyperpolarized 13C magnetic resonance spectroscopic imaging (HP-13C MRSI), to non-invasively monitor IRAK inhibition in PCNSL for the first time. Two PCNSL patient-derived xenografts models were studied: one harboring the L265P MYD88 mutation (MYD88mut), and the other, wild type for this protein (MYD88wt). Using HP-13C MRSI, a high production of HP [1-13C] lactate was detected in both MYD88wt and MYD88mut (0.5 ± 0.04, n=2 MYD88wt; 0.61 ± 0.2, n=4 MYD88mut), indicating PCNSL presence throughout the brain. At day 2 and 4 of AZ1495 treatment, the HP [1-13C] lactate-to-pyruvate ratio remains unchanged in MYD88wt animals at all treatment time points (p=0.29 and p=0.29 at day 2 and 4 when compared to baseline, respectively) On the other hand, this ratio significantly decreased in MYD88mut animals at all time points (36.6% at day 2, p=0.07 and 56.3% at day 4, p=0.0006), in line with the previously reported effect of AZ1495 treatment on MYD88mut PCNSL only. To conlude, we showed that HP-13C MRSI can detect MYD88-mutation-specific modulations of HP lactate production following IRAK inhibition. Because HP-13C MRSI is clinically translatable and expanding rapidly, this study is of high significance for future clinical trials, to enhance monitoring of PCNSL progression and response of targeted therapies.
MA 01.07 Lanreotide Maintenance in SCLC Expressing Somatostatine Receptors: Efficacy Results of Multicenter Randomized G04.2011 trial
Authors: S. Pilotto, E. Bria, D. Galetta, F. Grossi, G. Fasola, G. Romano, L. Bonanno, A. Bearz, M. Papi, A. Caprioli, A. Catino, A. Follador, E. Rijavec, A. Misino, G. Surico, A. Favaretto, L. Giannone, G. Tortora, D. Giannarelli, A. Santo
Journal: Journal of Thoracic Oncology (2017)
Vigilancia de la tuberculosis en la Región Europea de la OMS en 1.995: resultados del estudio de viabilidad
Authors: A Perrocheau, V Schwoebel, J Veen
Journal: Eurosurveillance (1998)

Los esfuerzos destinados a evaluar la cambiante epidemiologia de la tuberculosis (TB) en Europa se han visto limitados por las diferencias existentes entre las definiciones y la calidad de los sistemas de vigilancia de tuberculosis entre paises (1,2). A fin de estandarizar la vigilancia de la TB en los paises europeos, en 1.996 un grupo de trabajo formado por la Organizacion Mundial de la Salud (OMS) y la Union Internacional contra la Tuberculosis y las Enfermedades Respiratorias, que conto con la aprobacion de representantes de 37 paises, elaboro recomendaciones de consenso, incluida una definicion de caso frecuente y un conjunto minimo de variables a recoger (3,4).