tbuckley/cabot-search huggingface dataset:
PDTM-33. FOCUSED ULTRASOUND DISRUPTION OF THE BLOOD BRAIN BARRIER IN THE BRAINSTEM: A FEASIBILITY AND SAFETY STUDY
Authors: Saira Alli, Carlyn Figueredo, Nesrin Sabha, Megan Wu, Andrew Bondoc, Brian Golbourn, Amanda Luck, Christian Smith, Heiko Wurdak, Kullervo Hynynen, Meaghan O’Reilly, James Rutka
Journal: Neuro-Oncology (2017)

Magnetic Resonance Image-guided Focused Ultrasound (MRgFUS) has been used to achieve transient BBB opening without tissue injury. Delivery of a targeted ultrasonic wave causes an interaction between administered microbubbles and the capillary bed resulting in enhanced vessel permeability. The use of MRgFUS in the brainstem has not previously been shown. Using a rodent model, we have conducted a study demonstrating the safety of this technique in the brainstem. Four groups of rats were used: 1) Microbubble administration but no MRgFUS treatment; 2) MRgFUS only; 3) MRgFUS + microbubbles; and 4) MRgFUS + microbubbles + cisplatin. Physiological assessment was performed by monitoring of heart and respiratory rates. Motor function and co-ordination were evaluated by Rotarod and grip strength testing. Histological analysis for haemorrhage (H&E), neuronal nuclei (NeuN) and apoptosis (cleaved Caspase-3) was also performed following the ultrasound procedure. T1-weighted MR imaging confirmed BBB opening by contrast enhancement and positive Evans blue staining of the brainstem. The normal cardiorespiratory parameters were preserved, with grip strength and Rotarod testing demonstrating no difference in performance across all groups. Histological analysis showed no evidence of haemorrhage, neuronal loss or increased apoptosis. Our data confirm that we have identified parameters to safely, effectively and non-invasively open the BBB in the brainstem, giving promise towards therapeutic drug delivery to brainstem-specific conditions such as diffuse intrinsic pontine glioma (DIPG).
EXTH-58. EFFECTS OF TORC1/2 INHIBITOR MLN0128 ALONE AND IN COMBINATION WITH MEK INHIBITION IN BRAF MUTATED GLIOMA MODELS IN VITRO AND IN VIVO
Authors: Kevin X Liu, Sabine Mueller, Rogier Dik, Xiaodong Yang, Steven DuBois, Angela J Waanders, Adam C Resnick, William A Weiss, Daphne Haas-Kogan
Journal: Neuro-Oncology (2017)

MLN0128, a second-generation ATP-competitive pan-mTOR kinase inhibitor, acts on both mTORC1 and mTORC2. We investigated the effects of MLN0128 monotherapy and in combination with MEK and BRAFV600E inhibition in models of pediatric low-grade glioma (PLGG). We used human glioma cell lines expressing BRAFV600E (AM38), wild-type BRAF (LN229, TN98, SF188) and isogenic systems of KIAA1549:BRAF-expressing NIH3T3 cells. Signaling inhibitors included MLN0128, everolimus, BRAFV600E specific inhibitor PLX4720, and MEK specific inhibitors AZD6244 and GSK1120212. Cell proliferation was determined using an ATP-based assay. Biochemical effects were assessed using western blot analysis. The DBTRG (BRAFV600E) xenograft mouse model was used to assess in vivo efficacy. MLN0128 monotherapy demonstrates more potent anti-proliferative effects compared to everolimus in all tested PLGG lines independent of BRAF status. As expected, treatment with MLN0128 leads to down-regulation of p-AKT, p-S6 and p-4EBP1, whereas treatment with everolimus only reduces expression of p-S6. MEK inhibition with AZD6244 effectively decreases p-ERK expression in all lines; however, the addition of MLN0128 to AZD6244 causes a rebound in p-ERK expression in BRAFWT gliomas but not in gliomas expression BRAFV600E or KIAA1549:BRAF alterations. In cells carrying either the BRAFV600E or KIAA1549:BRAF alteration, combined treatment with MLN0128 and GSK1120212 or AZD6244 leads to synergistic anti-proliferative effects but such synergy is not evident in BRAFWT gliomas. In vivo studies show superior efficacy of combinations of PLX4720 and MLN0128 compared to monotherapies (p<0.02) or combination of PLX4720 + everolimus (p=0.03). MLN0128 displays synergistic anti-neoplastic effects with MEK inhibition in gliomas bearing BRAFV600E or KIAA1549:BRAF. In BRAF wild-type cells, such synergy is not present, potentially due to rebound in p-ERK when MLN0128 is combined with AZD6244. Combination therapy with MLN0128 + PLX4720 prolongs survival in a BRAFV600E mutant glioma model and is superior to monotherapy or everolimus + PLX4720 combination.
GENE-06. EXPRESSION OF LINC00152, A PUTATIVE SPONGE FOR TUMOR-SUPPRESSIVE micro-RNA, CORRELATES WITH GLIOMA GRADE
Authors: Soeren Mueller, Daniel He, Josie Hayes, Siyuan Liu, Martina Malatesta, Arnold Kriegstein, Manish Aghi, Daniel Lim, Aaron Diaz
Journal: Neuro-Oncology (2017)

Long noncoding RNAs (lncRNAs) play crucial roles in normal physiology as well as various disease states. We compared The Cancer Genome Atlas (TCGA) lower grade glioma (LGG, n=414) and glioblastoma (GBM, n=144) RNA-seq data and found only a few differentially expressed lncRNAs. The most significantly differentially expressed lncRNA was LINC00152. In an independent cohort (n=109 grade II, n=72 grade III, n=144 grade IV) LINC00152 expression was enriched in tumors with higher grade. In LGG, LINC00152 levels were negatively correlated with methylation of its promoter region (r=-0.69, p < 2.2e-16) and silencing was confirmed in single cell RNA-seq of 10 astrocytoma and 6 oligodendroglioma patients, where less than 0.3% of malignant cells express LINC00152. Furthermore, expression of LINC00152 was increased in IDH1 wild-type immortalized human astrocytes compared to astrocytes transfected with mutant IDH1, suggesting an association between LINC00152 promoter methylation and IDH1 mutation in primary LGG. Interestingly, comparing LINC00152 expression between matched primary and recurrent IDH1 mutant gliomas (n=53), we found significantly elevated expression in recurrent tumors (adj. p<9e-7). In glioblastoma, LINC00152 expression was significantly higher in mesenchymal compared to proneural GBMs (adj. p<0.01). In single cell RNA-seq of GBM biopsies of 7 patients, more than 60% of malignant single cells were positive for LINC00152 expression. Co-expression network analysis revealed a strong co-expression of LINC00152 with glioma cell proliferation markers. Furthermore, bioinformatic prediction of miRNA binding sites suggests that LINC00152 may act as a miRNA sponge for 20 miRNAs, 17 of which have been shown to be tumor suppressor miRNAs in glioma (ex. let-7, miR-153, miR-216).
Ensuring Access to Preventive Services for Adolescents
Authors: Abigail English, Jane Perkins
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-30. TREM1-TARGETED PET IMAGING OF TUMOR-ASSOCIATED MACROPHAGES IN AN ORTHOTOPIC GLIOBLASTOMA MOUSE MODEL
Authors: Emily Johnson, Surya Murty, Aaron Mayer, Connie Tsai, Swapnil Mehta, Ohad Ilovich, Tarik Massoud, Katrin Andreasson, Michelle James
Journal: Neuro-Oncology (2017)

Tumor-associated macrophages (TAMs) are key components of glioblastoma (GBM) cellular microenvironment. Triggering receptor expressed on myeloid cells 1 (TREM1) is a membrane receptor acting as a potent amplifier of proinflammatory responses and immune signaling. TREM1 is highly expressed on TAMs, but not cancer cells. Imaging TREM1 could provide a biomarker of functional status of myeloid cells in the context of glioma biology. We synthesized a TREM1-targeted PET tracer and evaluated its ability to detect TAMs in mice. We conjugated anti-TREM1 monoclonal antibody to DOTA, radiolabeled with 64Cu, and performed uptake and blocking studies in cell culture. We then evaluated [64Cu]TREM1-mAb in vivo using an orthotopic GL26 cell model in C57Bl/6 albino mice. One week after implantation, we injected mice with [64Cu]TREM1-mAb (~90mCi) and imaged one day later using PET/CT and MRI. Mice were then perfused to remove possible unbound intravascular [64Cu]TREM1-mAb, and radioactivity in dissected tissues was measured using a gamma-counter. Brain sections from selected GBM and sham mice were further analyzed via ex vivo digital autoradiography and stained with H&E. PET signal from brain tumors was significantly higher than observed in healthy brain regions or sham mice (tumor: 4.10 ± 0.67 %ID/g; normal brain: 1.74 ± 0.57 %ID/g; sham brain: 1.07 ± 0.17%ID/g; p<0.01, n=4). Similarly, biodistribution results revealed significantly higher tracer uptake in the whole brain of GBM mice compared to shams (0.35 ± 0.12 vs. 0.14 ± 0.02 %ID/g, p<0.05, n=4). Autoradiography also showed markedly higher [64Cu]TREM1-mAb binding within tumor compared to normal brain and sham brain slices. This is the first study of a PET tracer targeting TREM1. The ability to image TREM1 levels in vivo and home in on maladaptive immune responses in the GBM microenvironment could profoundly impact the way we understand the neuroinflammatory contribution to glioma biology, as well our ability to select and monitor potentially novel GBM therapies.
IMMU-35. TARGETING IDO1 IN HUMAN PEDIATRIC BRAIN CANCER
Authors: Kristen Lauing, Rishi Lulla, Alicia Lenzen, Lijie Zhai, Rintaro Hashizume, Jason R Fangusaro, Derek Wainwright
Journal: Neuro-Oncology (2017)

Indoleamine 2,3 dioxygenase 1 (IDO1) is a rate-limiting enzyme that converts tryptophan (Trp) into kynurenine (Kyn) and has been confirmed to suppress the immune response in adults diagnosed with malignant glioma. To address the role of IDO1 in pediatric high grade glioma (HGG), we investigated its expression in surgically-resected human pediatric HGG and in primary HGG cell lines that included diffuse intrinsic pontine glioma (DIPG). Utilizing qRT-PCR, two populations of gliomas were found based on high (>3 fold expression compared to control) versus low (<3 fold) IDO1 expression in patient tumor tissue. Notably, DIPG universally expressed low IDO1 levels when compared to HGG. In vitro, HGG cells inducibly expressed IDO1 protein and mRNA by 8 hours post-IFNγ treatment. At ≥250 nM, BGB-5777 [a novel, pharmaceutical-grade IDO1 enzyme inhibitor (Beigene)] significantly decreased the Kyn/Trp ratio in HGG and DIPG cell lines stimulated with IFNγ (P<0.001), while 250 nM – 1 µM L1-MT and D1-MT had no impact on Trp and Kyn levels. Unexpectedly, BGB-5777 induced a significant increase in IDO1 protein levels at 24 and 48 hours post-treatment. These data demonstrate that, IDO1 is expressed in pediatric HGG and can be targeted with an enzyme inhibitor, but that it unexpectedly leads to IDO1 protein stability. Given that IDO1 enzyme inhibitors are under evaluation in adults with brain cancer, these data suggest that BGB-5777 may be a valuable agent for future therapeutic consideration in children with malignant glioma.
Prognostic factors in unresectable biliary tract cancer: a GICO (Gruppo Italiano COlangiocarcinoma) retrospective analysis
Authors: F. Leone, R. Filippi, A. Palloni, L. Fornaro, A. Casadei Gardini, G. Aprile, N. Silvestris, M.A. Satolli, L. Faloppi, S. Daniele, E.S. Lutrino, C. Vivaldi, G.L. Frassineti, S.K. Garattini, O. Brunetti, M. Russano, M. Scartozzi, C. Cagnazzo, M. Aglietta, B. Giovanni
Journal: Annals of Oncology (2017)
Mass Administration of Ivermectin in Areas Where <i>Loa loa</i> Is Endemic
Authors: Frank O. Richards
Journal: New England Journal of Medicine (2017)

The 2015 Nobel Prize in Medicine was shared in part by the discoverers of ivermectin.1 Donated tablets of ivermectin have been distributed in Africa since 1988 through mass drug administration programs for onchocerciasis, or river blindness (caused by Onchocerca volvulus),2 and since 2000 for lymphatic filariasis (caused by Wuchereria bancrofti).3 These vectorborne filarial parasites cause disabling and stigmatizing diseases, especially in impoverished populations. The complex lifecycles of these parasites include male and female adult worm stages, in which fertilized females in humans release microfilariae that can be ingested by simulium black flies from the skin, in the case of onchocerciasis, . . .
Liver transplantation for hepatocellular carcinoma.
Authors: J McPeake, R Williams
Journal: Gut (1995)

Leading articleLiver transplantation for hepatocellular carcinoma As experience in orthotopic liver transplantation (OLT) has accumulated, it has become clear that frequent tumour recurrence has impaired overall survival figures for patients transplanted for hepatocellular carcinoma (HCC).In most series, two year survival has been 30% or lessl-5 and in the context of a limited supply of donor organs, the validity of continuing to transplant such cases has been called into question.3 6Some HCC patients do achieve a cure with OLT, in particular those in whom the tumour is an incidental one, being found only on examination of the explant.46These lesions are usually small, and tumour recurrence is less common -between O0/o-1 3% compared with 370/o-82% in cases where the diagnosis of HCC was established before operation.3 5 7 8In general, the smaller the tumour the less likely it is to recur, but in a few patients even with large tumours cure is obtained, as in an early case in the Cambridge/King's College Hospital series when the tumour weighed 4 kg.9Cases such as this add to the difficulty of decision making for the physician and patient who may feel that even the smallest chance of a cure is worth taking.
Desde la evaluación hasta el control de calidad continuo de los sistemas de vigilancia
Authors: G Krause
Journal: Eurosurveillance (2006)

Los sistemas de vigilancia fueron descritos como las « celulas nerviosas » de la salud publica, con brazos aferentes para recoger la informacion, « cuerpos celulares » donde se analiza y brazos eferentes para llevar a cabo las acciones apropiadas o diseminar la informacion [1]. 
La importancia de los sistemas de vigilancia tambien se manifiesta por el numero creciente de publicaciones cientificas sobre la metodologia y la evaluacion de estos sistemas. Las referencias mas citadas en esas publicaciones son la definicion de la Vigilancia en Salud Publica por Thacker y Berkelman [2], las variaciones de esa definicion y las recomendaciones para evaluar los sistemas de vigilancia desde las primeras en 1988 [3] y su actualizacion publicada en 2002 por grupos de trabajo del CDC (Centers for Disease Control and Prevention) en los Estados Unidos de America [4].
Rechallenge with cetuximab (cet) + irinotecan (iri) in 3rd-line in RAS and BRAF wt metastatic colorectal cancer (mCRC) patients (pts) with acquired resistance to 1st-line cet + iri: the phase II CRICKET study by GONO
Authors: D. Santini, C. Cremolini, L. Salvatore, S. Lonardi, E. Dell'Aquila, M. Cattaneo, F. Loupakis, D. Rossini, B. Vincenzi, S. Ziampiri, V. Buoro, E. Tamburini, D. Basile, D.C. Corsi, I. Fioroni, G. Masi, B. Borelli, M. Del Re, G. Tonini, A. Falcone
Journal: Annals of Oncology (2017)
Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres
Authors: Junseong Park, Jin-Kyoung Shim, Joon Hee Kang, Junjeong Choi, Jong Hee Chang, Soo-Youl Kim, Seok-Gu Kang
Journal: Neuro-Oncology (2017)

Targeted approaches for treating glioblastoma (GBM) attempted to date have consistently failed, highlighting the imperative for treatment strategies that operate on different mechanistic principles. Bioenergetics deprivation has emerged as an effective therapeutic approach for various tumors. We have previously found that cancer cells preferentially utilize cytosolic NADH supplied by aldehyde dehydrogenase (ALDH) for ATP production through oxidative phosphorylation (OxPhos). This study is aimed at examining therapeutic responses and underlying mechanisms of dual inhibition of ALDH and OxPhos against GBM. For inhibition of ALDH and OxPhos, the corresponding inhibitors, gossypol and phenformin were used. Biological functions, including ATP levels, stemness, invasiveness, and viability, were evaluated in GBM tumorspheres (TSs). Gene expression profiles were analyzed using microarray data. In vivo anticancer efficacy was examined in a mouse orthotopic xenograft model. Combined treatment of GBM TSs with gossypol and phenformin significantly reduced ATP levels, stemness, invasiveness, and cell viability. Consistently, this therapy substantially decreased expression of genes associated with stemness, mesenchymal transition, and invasion in GBM TSs. Supplementation of ATP using malate abrogated these effects, whereas knockdown of ALDH1L1 mimicked them, suggesting that disruption of ALDH-mediated ATP production is a key mechanism of this therapeutic combination. In vivo efficacy confirmed remarkable therapeutic responses to combined treatment with gossypol and phenformin. Our findings suggest that dual inhibition of tumor bioenergetics is a novel and effective strategy for the treatment of GBM.
A phase II trial of dacomitinib in locally advanced unresectable or metastatic skin squamous cell carcinoma
Authors: P. Bossi, S. Cavalieri, F. Perrone, R. Miceli, P. Ascierto, L. Locati, C. Bergamini, R. Granata, S. Alfieri, C. Resteghini, D. Galbiati, A. Busico, N. Paielli, R. Patuzzo, A. Maurichi, G. Gallino, R. Ruggeri, L. Mariani, M. Palla, L. Licitra
Journal: Annals of Oncology (2017)
Epidemia de fiebre Q en Lohra-Rollshausen, Alemania, primavera 1996
Authors: O Lyytikaïnen, T Ziese, B Schwartländer, P Matzdorff, C Kuhnhen, C Burger, W Krug, L R Petersen
Journal: Eurosurveillance (1997)

La fiebre Q (fiebre de Query) es una enfermedad febril aguda (y, a veces, cronica) causada por la rickettsia Coxiella burnetii. Los reservorios animales mas comunes de C. burnetii son el ganado vacuno, ovino y caprino. El organismo, que resiste la desecacion, se difunde particularmente por productos del parto de animales (tejidos placentarios, liquidos del parto). Las personas se infectan principalmente por la inhalacion de polvo y aerosoles contaminados (1). En mayo de 1996, el Servicio de Salud de Marburg-Biedenkopf de Hessen recibio informacion acerca de una agrupacion de pacientes con fiebre alta y persistente en Rollshausen y los pueblos de los alrededores. Las pruebas serologicas de algunos pacientes realizadas por las autoridades sanitarias locales indicaban que estas personas tenian fiebre Q.
P1.03-031 Adherence and Feasibility of 2 Treatment Schedules of S-1 as Adjuvant Chemotherapy in Completely Resected Lung Cancer
Authors: T. Kiribayashi, Y. Hata, K. Kishi, M. Nagashima, T. Nakayama, S. Ikeda, M. Kadokura, Y. Ozeki, H. Otsuka, Y. Murakami, S. Kusachi, K. Takagi, A. Iyoda
Journal: Journal of Thoracic Oncology (2017)
EXTH-33. TO ACHIEVE GREATER EFFICACY IN TUMOR-TREATMENT FIELDS: MODELING BASED ON THE INTRACELLULAR MECHANISMS
Authors: Kristen Carlson, Rohit Ketkar, Socrates Dokos
Journal: Neuro-Oncology (2017)

Despite invasive surgical resection of glioblastoma followed by radiotherapy and/or chemotherapy with concomitant side effects, most patients survive just 1 to 2 years, with no improvement in survival rates in over a decade. In contrast, low-intensity, alternating electric fields delivered non-invasively via scalp electrodes (tumor-treating fields, ‘TTFields’) lack side effects and combined with chemotherapy significantly increase glioblastoma patients’ survival without affecting quality of life. TTFields are in clinical trials for non-small lung cell, pancreatic, and ovarian cancers. To identify TTFields’ mechanisms, improve efficacy, and expand side-effect-free application to more cancer cell types we have built multi-purpose finite element models in COMSOL of TTFields’ effect on critical sub-cellular structures. It is well-established that TTFields interfere with rapidly-dividing cells’ mitotic processes, causing abnormal chromosome segregation, aneuploidy, and apoptosis, probably through multiple mechanisms. The sub-cellular targets of TTFields are likely high dipole-moment and polarizable molecules such as microtubules (MT) and septin, whose unperturbed functioning are critical to silencing cell cycle checkpoints and normal progression of mitosis. Our models allow quantitative investigation of physical interactions between the electric field and these structures, thereby gaining deep insight into the biophysics of TTFields. The models have revealed electric field amplification at MT ends, high current and high energy density in the counter-ion layers surrounding MT C-termini thought to be the critical MT signaling mechanism. These findings support TTFields’ reported mechanisms of action. We are currently testing mechanistic hypotheses posed by TTFields research teams, including: 1. Dislocalization of septins causing aberrant mitotic exit; 2. Mitotic spindle disruption leading to improper chromosome segregation and mitotic catastrophe; 3. Disruption of MT polymerization homeostasis. We encourage researchers to send us their hypotheses to test in our modeling.
P2.01-056 Use of Cell-Free Circulating RNA (cfRNA) Expression of PD-L1 and ERCC1 in Plasma to Monitor Response to Therapy in NSCLC
Authors: L. Raez, K. Danenberg, A. Castrellon, S. Rabizadeh, J. Usher, Y. Jaimes, B. Hunis, M. Dietrich, C. Habaue, P. Danenberg
Journal: Journal of Thoracic Oncology (2017)