tbuckley/cabot-search huggingface dataset:
CMET-09. PAN-CANCER PROFILES OF BRAIN METASTASES: PRIORITIZATION OF THERAPEUTIC TARGETS
Authors: Sherise Ferguson, Siyuan Zheng, Joanne Xiu, Shouhao Zhou, Mustafa Khasraw, Priscilla K Brastianos, Santosh Kesari, Jethro Hu, Jeremy Rudnick, Michael Salacz, David Piccioni, Huang Suyun, Micheal Davies, Isabella Glitza, John Heymach, Jianjun Zhang, Nuhad Ibrahim, John de Groot, Joseph McCarty, Barbara J O’Brien, Raymond Sawaya, Roel Verhaak, Sandeep Reddy, Waldemar Priebe, David Spetzler, Amy Heimberger
Journal: Neuro-Oncology (2017)

Metastasis is the most common source of tumors in the brain. Despite their prominence, the biology of brain metastases remains poorly understood making prognosis poor and the need for additional treatment options is urgent. We performed targeted genetic profiling of primary tumors and metastases (brain and systemic) to elucidate brain-associated alterations and prioritize potential targets for brain metastasis treatment. Tumor profiling involved multiplatform analyses including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (immunohistochemistry) and gene amplification of 16,999 unmatched primary/metastasis samples: 8178 non-small cell lung cancers (5098 primaries; 2787 systemic metastases; 293 brain metastases), 7064 breast cancers (3496 primaries; 3469 systemic metastases; 99 brain metastases), and 1757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). Across pathologies, TOP2A, which controls and alters the topologic states of DNA during transcription, was the most frequently expressed protein in brain metastasis relative to the primary (NSCLC: 74.5% versus 55%, P <0.0001; breast cancer: 78.8% versus 50.1%, P = 0.0001; melanoma: 76.4% versus 45.8%, P=0.0011). Two additional enzymes involved in DNA synthesis and chemoresistance, RRM1, and TS, were also increased in NSCLC brain metastases relative to the primary (31.8% versus 20.9%, P = 0.0049; and 34.9% versus 21.5%, P = 0.0006, respectively). Other DNA topoisomerases and enzymes essential for DNA replication/repair such as TOPO1 (77.9% versus 63.4%, P = 0.0357) and ERCC1 (61.8% versus 42.1%, P= 0.0199) were also more frequently expressed in breast cancer brain metastases. Unique to melanoma brain metastases was increased cMET expression frequency relative to the primary (36.4% versus 7.9%, P=0.0003). We report enriched expression of markers associated with DNA synthesis, replication, and repair in brain metastases compared with primary cancer specimens. This trend occurred across all tumor histologies, supporting the prioritization of therapies that target these pathways.
CMET-13. RADIATION THERAPY PATTERNS OF CARE FOR NON-SMALL CELL LUNG CANCER BRAIN METASTASES: AN ANALYSIS OF THE NATIONAL CANCER DATABASE
Authors: Caleb Dulaney, John Fiveash, Peng Li, Hunter Boggs
Journal: Neuro-Oncology (2017)

Radiation therapy for brain metastases has evolved recently with multiple randomized trials showing similar survival and better neurocognitive outcomes with stereotactic radiosurgery (SRS) compared to whole brain radiation (WBRT). However, there is limited data describing practice changes across the country. The purpose of this study is to describe changes in SRS and WBRT utilization in patients with non-small-cell lung cancer (NSCLC) in the National Cancer Database (NCDB). Patients presenting with brain metastases at diagnosis of NSCLC and who received brain radiation in the NCDB were identified from 2010–2014. Demographic, clinical, and facility characteristics were collected and compared. Overall survival, thirty-day mortality, and ninety-day mortality following diagnosis were calculated and compared using Kaplan-Meier survival statistics. Among patients diagnosed with NSCLC, 54,711 (10.8%) had brain metastases, and 31,379 (57.3%) received brain-directed radiation. Patients receiving SRS were younger and more likely to have private insurance, higher socioeconomic status, and to have traveled >50 miles to the treatment facility. From 2010 to 2014, the absolute and proportional utilization of SRS increased over time from 10.4% to 23% while WBRT utilization declined. Use of WBRT declined from 84% to 70% in academic centers and 93% to 81% in other centers. Over the same time, SRS usage increased from 16 to 30% in academic centers and 8% to 20% in other centers. Median survival was significantly longer for patients receiving SRS (11.9 months) versus WBRT (5.3 months). Thirty and ninety-day mortality were also significantly lower for SRS (0.8% and 8.3%) than for WBRT (3.1% and 25.4%). This study demonstrates 2–3 fold increase in SRS utilization, particularly in academic centers, for patients with NSCLC brain metastases. Because patients of higher socioeconomic status were more likely to receive SRS, future work should explore potential disparities and barriers to SRS utilization.
CSIG-42. UNDERSTANDING THE ROLE OF TRANSLATIONAL CONTROL IN MYCN-DRIVEN MEDULLOBLASTOMA
Authors: Ozlem Aksoy, Qiwen Fan, Kevan Shokat, Davide Ruggero, William Weiss
Journal: Neuro-Oncology (2017)

Medulloblastoma is the most common malignant brain tumor in children. While ~75% of patients survive more than 5 years, survivors have significant neurocognitive and neuroendocrine disabilities. MB is comprised of 4 distinct molecular subgroups (WNT, SHH,Group 3 and Group 4) differing in mutational spectra, gene expression signatures and clinical features including outcome. The proto-oncogene MYCN drives SHH subtype medulloblastoma, and when amplified, also marks the most aggressive and lethal subtype of medulloblastoma. Since MYCN is undruggable, understanding mechanisms through which MYCN-drives tumors promises to improve prognosis and quality of life for children with high-risk medulloblastoma. MYCN is a major regulator of translation control, and mTOR, a serine threonine kinase, represents a key node through which MYCN can potentially regulate translation. Our lab found that MYCN disrupts the translational apparatus to drive transformation. Also, by using different genetic and pharmacological methods to inhibit mTOR pathway, we leverage the interaction between MYCN and mTOR to identify downstream targets of this pathway in MYCN-driven medulloblastoma.
MA 19.07 Does Loss of Smad7 Lead to Increased Aggressiveness of Malignant Pleural Mesothelioma?
Authors: J. Gerstmayr, E. Lang, D. Falch, C. Pirker, V. Laszlo, B. Dome, W. Klepetko, M. Hoda, W. Berger, M. Grusch
Journal: Journal of Thoracic Oncology (2017)
Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex
Authors: Rui Feng, Jing Li, Jiepeng Chen, Lili Duan, XinRong Liu, Donghua Di, Yihui Deng, Yanzhi Song
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Nattokinase (NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK, nattokinase-tauroursodeoxycholate (NK-TUDCA) complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state, tail injury, and the body weight of mice, it was found that the NK-TUDCA complex (NK: 10 kIU/ml; TUDCA: 10 mg/ml; pH 5.0) had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the
Abstract 377: A Systematic Review of Medication Adherence Among African American Heart Failure Patients
Authors: Lila de Tantillo, Rosa M Gonzalez-Guarda
Journal: Circulation Research (2016)

Background: Heart failure is a leading cause of death in the United States and a condition of particular concern for the African American population. Although effective treatments are available for the disease, medication adherence is a key determinant of survival. Objective: This systematic review examines articles from the last 15 years that research medication adherence and African American heart failure patients. Methods: A systematic review of the published literature was conducted to identify articles examining predictors and outcomes of medication adherence among African Americans and then using Sister Callista Roy’s Health Adaptation conceptual framework - physiological, self-concept, role function and interdependence. Results: This review identified 14 articles that met inclusion criteria, most of which focused on physiological predictors, noting that age and comorbid conditions such as dialysis status may play a role in medication adherence. Psychological, cultural and social determinants were also found to impact adherence behaviors. Conclusions: More research is needed to examine other components of the Health Adaptation model, especially socioeconomic and healthcare system level predictors.
L’impact de la vague de chaleur sur la mortalité journalière en Angleterre et Pays de Galles et l’utilisation de calculs de mortalité hebdomadaires rapides
Authors: H Johnson, S Kovats, G McGregor, J Stedman, M Gibbs, H Walton
Journal: Eurosurveillance (2005)

L’article suivant decrit une analyse retrospective de l’impact de la vague de chaleur de 2003 sur la mortalite en Angleterre et au Pays de Galles et la compare avec les calculs rapides bases sur le systeme de notification en routine des deces hebdomadaire.
TMOD-02. IDENTIFICATION OF NOVEL MARKERS OF TREATMENT-REFRACTORY RECURRENT GLIOBLASTOMA
Authors: Nicolas Yelle, Chirayu Chokshi, Parvez Vora, Chitra Venugopal, Sheila Singh
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is a very aggressive and invasive tumor that relapses within nine months of diagnosis and remains incurable despite advances in multimodal therapy including surgical resection, chemotherapy and radiation. Poor patient outcome has been linked to both marker expression of brain tumor initiating cells (BTICs) and intratumoral heterogeneity (ITH), which have been associated with treatment resistance and tumor recurrence. ITH can be explained at the cellular level by the existence of multiple populations of cancer cells, including some which have acquired stemness properties like self-renewal, proliferation, and multilineage differentiation, also known as cancer stem cells (CSCs). In brain tumors, CSCs or BTICs, have been shown to be resistant to both chemotherapy and radiation treatment, allowing them to escape therapy and consequently allowing for tumor recurrence. As a result, therapies that focus on targeting the BTIC compartment within the bulk GBM tumor would provide better treatment and prognosis for patients. To profile ITH as it evolves through therapy delivery, we have developed a novel and dynamic BTIC patient-derived xenograft (PDX) model of human GBM recurrence, which allows for multimodal profiling of GBM BTICs at engraftment, after chemoradiotherapy delivery in a phase we have termed “minimal residual disease” (MRD), and at tumor recurrence. In this study, we present the profiling of the transcriptome and the cell-surface proteome at each of these stages, including validation of targets, novel and exclusive to recurrent treatment-refractory GBM, by CRISPR/Cas9 knockout and subsequent functional stem cell assays. Despite the fact that recurrent GBM is what ultimately leads to patient demise, it remains a largely unknown landscape. Virtually all of the current genomic, transcriptomic, and proteomic data is based on primary GBM. Hence, our study provides a unique therapeutic window into the often-overlooked elephant in the room: recurrent glioblastoma.
The Imminent Demise of Cardiovascular Drug Development
Authors: Milton Packer
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
P1.15-017 Adoption of Prophylactic Cranial Irradiation for Extensive Stage Small Cell Lung Cancer: A Population Based Outcomes Study
Authors: Y.Y. Soon, H. Zheng, S. Ho, S.P. Yap, W.Y. Koh, C.N. Leong, B. Vellayappan, J. Tey, K.W. Fong, I. Tham
Journal: Journal of Thoracic Oncology (2017)
ADS 5102 (Amantadine) Extended Release for Levodopa-Induced Dyskinesia—Reply
Authors: Aparna Wagle Shukla
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
L'étude d'EUVAC-NET sur les systèmes de surveillance nationaux de la coqueluche dans l’Union européenne, en Suisse, en Norvège et en Islande
Authors: J E Schmidt, A E Tozzi, L Rava, S Glismann
Journal: Eurosurveillance (2001)

Par le biais d'un questionnaire envoye aux Etats membres de l'Union Europeenne (UE), ainsi qu'en Suisse, en Norvege et en Islande, une enquete a ete menee sur le type d'informations recueillies en routine par les systemes de surveillance nationaux de la coqueluche. Cette etude portait sur les methodes de surveillance, les informations enregistrees pour les cas de coqueluche, le calendrier vaccinal, le type de vaccin utilise et les methodes d'evaluation de la couverture vaccinale. Il existe de grandes variations entre les pays participants, mais les resultats de l'enquete montrent l'existence de sous-groupes de variables communs a de nombreux pays. Les prochaines activites d’EUVAC-NET consisteront a definir des elements homogenes dans les systemes nationaux et a regrouper de facon pertinente les pays presentant des caracteristiques communes de surveillance.
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation
Authors: Alison C. McGarvey, Stanislav Rybtsov, Céline Souilhol, Sara Tamagno, Ritva Rice, David Hills, Duncan Godwin, David Rice, Simon R. Tomlinson, Alexander Medvinsky
Journal: The Journal of Experimental Medicine (2017)

In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development. We demonstrate that BMPER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMPER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture.
IMMU-15. PD-1 BLOCKADE ACTIVATES CD4 T CELLS AND THE INNATE IMMUNE RESPONSE FOR GLIOBLASTOMA ERADICATION
Authors: Sarah R Klein, Maria Carmela Speranza, Prafulla C Gokhale, Margaret K Wilkens, Kristen L Jones, Paul T Kirschmeier, Apoorvi Chaudhri, David Reardon, Gordon J Freeman
Journal: Neuro-Oncology (2017)

Blockade of immune cell co-inhibitory receptor PD-1 using monoclonal antibodies (mAbs) allows the development of anti-tumor immunity in various solid tumors and lymphoid malignancies. We recently demonstrated that PD-1 blockade elicits an anti-tumor immune response resulting in tumor rejection and long-term survival in approximately 50% of mice with intra-cranial GL-261 glioblastoma, despite the absence of accumulating CD8+ cytotoxic T cells in the tumor or draining lymph nodes. In this investigation, we provide evidence for the role of conventional CD4+ T cells and the innate immune response in PD-1 mediated anti-glioma immunity in this model. In response to anti-PD-1 monotherapy, intratumoral CD4+ T cells, but not CD8+ T cells, expressed significantly elevated levels of IFN-γ and TNF-α pro-inflammatory cytokines and the cytotoxic enzyme, granzyme B. Tbet, GATA3, and EOMES, transcription factors required for T cell proliferation, activation, and effector function, were also up-regulated in CD4+, but not CD8+ T cells in the brains of mice treated with PD-1 mAbs when compared to controls. We demonstrated that depletion of CD4+ or CD8+ T cells, but not NK, was sufficient to completely ablate anti-PD-1-mediated tumor eradication and long-term survival. CD4+ T cell activation was accompanied by the classical activation and M1 polarization of resident microglia and tumor-infiltrating macrophages. Moreover, CSF-1 inhibition with PLX3397 to deplete microglia and macrophages did not affect tumor growth, but did lead to a significant survival advantage when combined with anti-PD-1 mAb. Together, these studies demonstrate for the first time a role for CD4+ T cells and the innate immune response in the eradication of glioblastoma by PD-1 blockade.
Volumetric analysis of IDH-mutant lower-grade glioma: a natural history study of tumor growth rates before and after treatment
Authors: Raymond Y Huang, Robert J Young, Benjamin M Ellingson, Harini Veeraraghavan, Wei Wang, Florent Tixier, Hyemin Um, Rasheed Nawaz, Tracy Luks, John Kim, Elizabeth R Gerstner, David Schiff, Katherine B Peters, Ingo K Mellinghoff, Susan M Chang, Timothy F Cloughesy, Patrick Y Wen
Journal: Neuro-Oncology (2020)

Abstract Background Lower-grade gliomas (LGGs) with isocitrate dehydrogenase 1 and/or 2 (IDH1/2) mutations have long survival times, making evaluation of treatment efficacy difficult. We investigated the volumetric growth rate of IDH mutant gliomas before and after treatment with established glioma therapies to determine whether a significant change in growth rate could be documented and perhaps be used in the future to evaluate treatment response to investigational agents in LGG trials. Methods In this multicenter retrospective study, 230 adult patients with IDH1/2 mutated LGGs (World Health Organization grade II or III) undergoing surgery, radiation, or chemotherapy for progressive non-enhancing tumor were identified. Subjects were required to have 3 MRI scans containing T2/fluid attenuated inversion recovery imaging spanning a minimum of 6 months prior to treatment. A mixed-effect model was used to estimate tumor growth prior to treatment. A subset of 95 patients who received chemotherapy, radiotherapy, or chemoradiotherapy and had 2 posttreatment imaging time points available were evaluated for change in pre- and posttreatment volumetric growth rates using a piecewise mixed model. Results The pretreatment volumetric growth rate across all 230 patients was 27.37%/180 days (95% CI: [23.36%, 31.51%]). In the 95 patients with both pre- and posttreatment scans available, there was a significant difference in volumetric growth rates before (26.63%/180 days, 95% CI: [19.31%, 34.40%]) and after treatment (−15.24% /180 days, 95% CI: [−21.37%, −8.62%]) (P &amp;lt; 0.0001). The growth rates for patient subgroup with 1p/19q codeletion (N = 118) was significantly slower than the rate of the 1p/19q non-codeleted group (N = 68) (22.84% vs 35.49%, P = 0.0108). Conclusion In this study, we evaluated the growth rates of IDH mutant gliomas before and after standard therapy. Further study is needed to establish whether a change in growth rate is associated with patient survival and its use as a surrogate endpoint in clinical trials for IDH mutant LGGs.
Efficacy of pertuzumab in combination with trastuzumab and a taxane in in first line treatment for metastatic breast cancer (MBC): a multicenter retrospective observational study
Authors: L. Mentuccia, A. Gelibter, I. Sperduti, L. D'Onofrio, A. Botticelli, P. Vici, A. Cassano, L. Moscetti, L. Carbognin, V. Graziano, G. Barchiesi, E. Rossi, M.C. Cursano, L. Pizzuti, I. Paris, A. Vaccaro, A. Fabbri, L. Rossi, R. Samaritani, R. Sarmiento, T. Gamucci
Journal: Annals of Oncology (2017)
P3.04-012 Phase 1 Study of the AXL Inhibitor DS-1205c in Combination with Osimertinib in Subjects with Metastatic or Unresectable EGFR-Mutant NSCLC
Authors: P. Jänne, H. Yu, M. Vigliotti, N. Shipitofsky, J. Li, J. Mcgill, C. Yu
Journal: Journal of Thoracic Oncology (2017)