tbuckley/cabot-search huggingface dataset:
TMIC-52. REACTIVE ASTROCYTES AID THE EVOLUTION OF IMMUNOSUPPRESSIVE ENVIRONMENT AND DRIVE ONCOGENIC SIGNALING IN GLIOBLASTOMA
Authors: Dieter Heiland, Vidhya Ravi, Simon P Behringer, Julian Wurm, Juergen Beck, Oliver Schnell
Journal: Neuro-Oncology (2019)

Abstract Reactive astrocytes are caused by multiple pathologies of the central nervous system, whereby they undergo distinct transcriptomic re-programming. Although the role of reactive astrocytes in some inflammatory diseases has been investigated, many central questions regarding the immunoregulatory functions of tumor-associated astrocytes and their crosstalk to microglia remain poorly understood. In our presented study, we purified astrocytes from various pathologies and different brain tumors to map the transcriptional landscape of reactive astrocytes. We identified the marker genes CHI3L1 and CD274 highly enriched in reactive astrocytes of the marginal astrogliosis scar at the tumor boarder. Human neocortical slices along with a microglia loss-of-function model were used to explore the crosstalk of microglia and reactive astrocytes within the tumor environment. Our results revealed that the reactive phenotype mutually arises from both, microglia and tumor cells. This interaction caused JAK/STAT signalling in reactive astrocytes along with a large release of anti-inflammatory cytokines such as TGFß and IL10. Additionally, inhibition of the JAK/STAT pathway recovered the release of anti-inflammatory cytokines and resulted in a pro-inflammatory environment. Besides the immunosuppressive properties, we found evidence that reactive astrocytes drove AKT and MAPK signaling in the tumor through astrocytic released CHI3L1 and consequential binding to IL13RA2. Our findings revealed increased malignant properties arising from astrocytic-tumor interaction, which were rescued by IL13RA2 inhibition. In a nutshell, reactive astrocytes have decisive regulatory tasks in the microenvironment of CNS tumors. Along with microglia, reactive astrocytes cause the evolution of an immunosuppressive environment and support malignant properties of the tumor.
Ex Vivo Expansion with E478 Increases the Rate of CRISPR-Mediated Homology Directed Repair of the Beta-Globin Gene in Human Hematopoietic Stem Cells By &gt;10-Fold and Improves In Vivo Engraftment By &gt;120-Fold
Authors: Kevin A. Goncalves, Megan D. Hoban, Sharon L. Hyzy, Katia S. George, Anthony E. Boitano, Michael P. Cooke
Journal: Blood (2019)
Chemotherapeutic management of adrenocortical carcinoma: The M. D. Anderson Cancer Center experience
Authors: G. G. Fareau, R. Vassilopoulou-Sellin
Journal: Journal of Clinical Oncology (2006)

14592 Background: Adrenocortical carcinoma (ACC) is a rare cancer associated with a poor prognosis. We describe our experience with the effectiveness of various chemotherapies in the treatment of ACC. Methods: We performed a detailed retrospective review of every patient diagnosed with ACC at the M.D. Anderson Cancer Center between the years 1980 and 2000. We included only those patients with a histological diagnosis of ACC who had radiologically measurable disease and received chemotherapy followed by post-treatment imaging. Patients without a pathological diagnosis, serial imaging studies, or adequate follow-up were excluded from our study. In each case, we compared radiological tumor burden after a given drug or drug combination to the radiological tumor burden preceding the treatment session. Radiologist reports were used to categorize post-treatment imaging studies as showing either a decrease in tumor burden, no change in tumor burden, or an increase in tumor burden. Patients who did not have post-treatment imaging due to rapid progressive clinical deterioration were regarded as having increased tumor burden. Results: 224 patients with a diagnosis of ACC were identified in our database, of which 62 had histological confirmation and received chemotherapy with documented radiological follow-up. 38 different chemotherapeutic regimens were reviewed. Patients given single agent fluorouracil, taxol, taxotere, trimetrexate, navelbine, and patients given combination treatment with cyclophosphamide/adriamycin/cisplatin, gemcitabine/taxotere, and mitotane/cisplatin/taxol did not show any improvement. Treatment with single agent mitotane and combination VP-16/cisplatin resulted in either no change or decrease in tumor burden in over 50% of sessions. Promising trends were seen in patients treated with single agent VP-16 and carboplatinum, and with combination adriamycin/cisplatin/ifosfamide, mitotane/cisplatin, and VP-16/adriamycin/cisplatin. Conclusions: We have identified specific drugs and drug combinations of no apparent benefit in this cohort, and have also identified select agents and combinations which offer benefit. Further prospective clinical trials should focus on the use of those agents and combinations which offer benefit. No significant financial relationships to disclose.
Effect of Metabolic Traits on the Risk of Cirrhosis and Hepatocellular Cancer in Nonalcoholic Fatty Liver Disease
Authors: Fasiha Kanwal, Jennifer R. Kramer, Liang Li, Jianliang Dai, Yamini Natarajan, Xian Yu, Steven M. Asch, Hashem B. El‐Serag
Journal: Hepatology (2019)

Nonalcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD.We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between January 1, 2004, and December 31, 2008, with follow-up through December 31, 2015. We performed competing risk-adjusted cause-specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow-up. At baseline, the mean body mass index was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% had hypertension, and 62.3% had dyslipidemia with substantial overlap among these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared with patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8-fold higher risk of progression to cirrhosis/HCC (hazard ratio [HR] = 1.8, 95% confidence interval [CI] = 1.59-2.06); the risk was 2.6-fold higher in patients with diabetes, obesity, dyslipidemia, and hypertension (HR = 2.6, 95% CI = 2.3-2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort.Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Patients with diabetes and coexisting hypertension and obesity may be important targets for secondary prevention.
Detecting therapy-guiding aberrations in platelets and plasma at the transcriptome level in non-small-cell lung cancer
Authors: P. Meng, A.A. Rybczynska, J. Wei, M.M. Terpstra, W. Timens, E. Schuuring, T.J.N. Hiltermann, H.J.M. Groen, K. Kok, A.J. Van der Wekken, A. Van den Berg
Journal: Annals of Oncology (2019)
Annals Story Slam - The Conversations We Have After Midnight
Authors: Lee Harel-Sterling
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 November 2019Annals Story Slam - The Conversations We Have After MidnightFREELee Harel-Sterling, MDLee Harel-Sterling, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0026 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - The Conversations We Have After Midnight "The Conversations We Have After Midnight," by Lee Harel-Sterling, MD (Duration 4:57)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 November 2019Volume 171, Issue 9Page: SS1 ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Patient Preferences Regarding Anticoagulation Therapy in Patients with Cancer Having a VTE Event - a Discrete Choice Experiment in the Cosimo Study
Authors: Nils Picker, Alexander T Cohen, Anthony Maraveyas, Jan Beyer-Westendorf, Agnes Yuet Ying Lee, Lorenzo G Mantovani, Yoriko De Sanctis, Khaled Abdelgawwad, Samuel Fatoba, Miriam Bach, Thomas Wilke
Journal: Blood (2019)
Quantitative Immunoprecipitation Free Light Chain Mass Spectrometry (QIP-FLC-MS) Simplifies Monoclonal Protein Assessment and Provides Added Clinical Value in Systemic AL Amyloidosis
Authors: Faye Amelia Sharpley, Hannah Victoria Giles, Richa Manwani, Shameem Mahmood, Sajitha Sachchithanantham, Helen J Lachmann, Julian D Gillmore, Carol J Whelan, Philip N Hawkins, Ashutosh D Wechalekar
Journal: Blood (2019)
GENE-41. UNDERSTANDING THE DIFFERENCES IN ADOLESCENT AND YOUNG ADULT (AYA) GLIOMAS AND OLDER ADULT (OA) GLIOMAS BASED ON FUNCTIONAL MOLECULAR SUBGROUPS
Authors: Catherine Bi, Ashwin Subramaniam, Joanne Xiu, Amy Heimberger, Sharon Michelhaugh, Sandeep Mittal, Ashley Sumrall, Deepa Subramaniam
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Gliomas in the AYA population (15–39 years of age) have unique biological characteristics and need to be better characterized. METHODS Glioma tumors in AYA subjects and subjects &gt;65 years of age (OA) were analyzed by next generation sequencing using a 592 gene panel. Pathogenic mutations were classified into five functional groups, viz. metabolic pathways genes (IDH1/2, FH), tumor suppressor genes (TP53, RB1, APC, NF1/2, PTEN, TSC1/2), genes involved in DNA repair (MMR genes, BRCA1/2, POLE, ARID1A, CHEK2, ATM, BLM, BRIP1, WRN, BARD1, POT1, MUTYH), oncogenes (BRAF, NRAS, HRAS, EGFR, PDGFRA, FGFR1, NOTCH1, MYCN), and genes involved in transcriptional regulation (SETD2, H3F3A, KMTD2A/2C/2D, KDM6A, PIK3CA). Mutation frequency in AYA tumors and OA tumors were compared using Chi-squared analysis (Pearson’s score χ2; likelihood ratio LR). RESULTS 720 unique gliomas tumors were analyzed: 118 AYA, 602 OA; 420 males, 300 females. When both groups are considered together, glioblastoma was the most common histology (75%), followed by grade 3 astrocytoma (13%), glioma NOS (3.8%), oligodendrogliomas (3%), low grade gliomas (2.9%) and other (2.3%). AYA tumors harbored more metabolic pathway gene mutations (χ2 137.7, p&lt; 0.0001) driven primarily by IDH1 mutations, while OA tumors had a higher mutation frequency in oncogenes (χ2 9.22, p=0.0024) driven by EGFR mutations (LR 27.567) and tumor suppressor genes (χ2 40.35, p&lt; 0.0001) driven by NF1 (LR 18.147) and PTEN (LR 66.216). No significant differences were noted in mutation frequency in DNA repair or transcriptional regulation genes. However, AYA glioblastoma tumors had a significant increase in mutations in genes involved in chromatin remodeling, (χ2 11.43, p=0.0007) even after excluding H3F3A. CONCLUSIONS Functional genomic classification of AYA tumors may help develop better targeted therapies, especially focused on genes involved in metabolic pathways and transcriptional regulation.
P1.07 Habits in Tobacco Consumption of a Population of Queretaro
Authors: K.L. García-Mejía, A.L. Vega-Rodríguez, A.G. Alcázar-Ramos, R. Salas-Coronado, N.F. Santos-Sánchez, B. Hernández-Carlos, M.D.P. Figueroa-Corona, M.A. Meraz-Ríos, K.I. Lira-De León
Journal: Journal of Thoracic Oncology (2019)
P16, c-Myc, SOX11, P53, ki67 and CD71Protein Expression in Aggressive Morphological Variants of Mantle Cell Lymphomas Compared to Classical Morphological Mantle Cell Lymphomas in Multiple Clinical Trials
Authors: Barbara Burroni, Anne Moreau, Mathieu Baldacini, Antoine Martin, Steven Le Gouill, Vincent Ribrag, Rémy Gressin, Chantal Brochet, Martin H. Dreyling, Samuel Griolet, Yannick Le Bris, Morgane Cheminant, Hanneke Kluin-Nelemans, Olivier Hermine, Luc Mathieu Fornecker, Alexandra Traverse-Glehen, Danielle Canioni
Journal: Blood (2019)
Clinical Relevance of MYC/BCL2 and Cell of Origin in Patients with Relapsed Diffuse Large B-Cell Lymphoma Treated with Autologous Stem Cell Transplantation
Authors: Yingjun Wang, Ken H. Young, Denái R. Milton, Celina Ledesma, Elias Jabbour, Zijun Yidan Xu-Monette, Jeffrey J. Molldrem, Paolo Anderlini, Amin M. Alousi, Qaiser Bashir, May Daher, Luis E. Fayad, Swaminathan P. Iyer, Partow Kebriaei, David Marin, Rohtesh S. Mehta, Amanda L. Olson, Uday Popat, Felipe Samaniego, Jason R. Westin, Muzaffar H. Qazilbash, Jin S Im, Gabriela Rondon, Alison Gulbis, Richard E. Champlin, Issa F. Khouri
Journal: Blood (2019)
SCIDOT-47. EFFECT OF ulRFE COGNATES EMULATING BIOACTIVE SUBSTANCES ON ANIMAL BEHAVIOR
Authors: Xavier Figueroa, Mike Butters, Scott Donnell
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The EMulate Therapeutics Voyager system produces a magnetic field obtained from the magnetic fluctuations produced by molecules in solution. These recordings, ultra-low radio frequency energy (ulRFE®) cognates, are intended to emulate the effects of the molecule. METHODS Mice were treated with cognates for up to 120 min on the first day, then 24 h/day for the next 15 days. RESULTS All ulRFE cognates were well tolerated. Body weights remained stable. Animals exposed to signals derived from melatonin, THC (tetrahydrocannabinol), scotch, and ethanol showed signs of mild hypo-activity, while cognates derived from CBD (cannabidiol), Everclear, nicotine, and white wine showed mild signs of somnolence. Caffeine exposure initially caused mild hyperactivity, which returned to normal after the 120 minutes. The espresso cognate induced signs of mild hyperactivity during the initial 20-minute exposure. After 40 minutes, mild head convulsions and normal activity levels were noted. After 120 minutes, signs of hypoactivity were seen. Animals exposed to caffeine ulRFE showed signs of mild hyperactivity for the duration of the 15-day exposure, and animals exposed to nicotine, melatonin, THC, CBD, Everclear, scotch, and white wine cognates experienced mild hypo-activity. Animals exposed to espresso or 100% ethanol ulRFE remained normal during the 15-day exposure. CONCLUSIONS Mice displayed altered behavior when exposed to the magnetic field produced by the cognates, which, at least in part, were consistent with some effects that would be anticipated for the molecules used to create the cognates. The ulRFE technology offers potential to emulate the effects of bioactive substances across the blood:brain barrier.
EXTH-02. THE BLOOD BRAIN BARRIER (BBB) PERMEABILITY IS ALTERED BY TUMOR TREATING FIELDS (TTFIELDS) IN VIVO
Authors: Ellina Schulz, Almuth F Kessler, Ellaine Salvador, Dominik Domröse, Malgorzata Burek, Catherine Tempel Brami, Tali Voloshin Sela, Moshe Giladi, Ralf-Ingo Ernestus, Mario Löhr, Carola Förster, Carsten Hagemann
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE For glioblastoma patients Tumor Treating Fields (TTFields) have been established as adjuvant therapy. The blood brain barrier (BBB) tightly controls the influx of the majority of compounds from blood to brain. Therefore, the BBB may block delivery of drugs for treatment of brain tumors. Here, the influence of TTFields on BBB permeability was assessed in vivo. METHODS Rats were treated with 100 kHz TTFields for 72 h and thereupon i.v. injected with Evan’s Blue (EB) which directly binds to Albumin. To evaluate effects on BBB, EB was extracted after brain homogenization and quantified. In addition, cryosections of rat brains were prepared following TTFields application. The sections were stained for tight junction proteins Claudin-5 and Occludin and for immunoglobulin G (IgG) to assess vessel structure. Furthermore, serial dynamic contrast-enhanced DCE-MRI with Gadolinium contrast agent was performed before and after TTFields application. RESULTS TTFields application significantly increased the EB accumulation in the rat brain. In TTFields-treated rats, the vessel structure became diffuse compared to control cryosections of rat brains; Claudin 5 and Occludin were delocalized and IgG was found throughout the brain tissue. Serial DCE-MRI demonstrated significantly increased accumulation of Gadolinium in the brain, observed directly after 72 h of TTFields application. The effect of TTFields on the BBB disappeared 96 h after end of treatment and no difference in contrast enhancement between controls and TTFields treated animals was detectable. CONCLUSION By altering BBB integrity and permeability, application of TTFields at 100 kHz may have the potential to deliver drugs to the brain, which are unable to cross the BBB. Utilizing TTFields to open the BBB and its subsequent recovery could be a clinical approach of drug delivery for treatment of brain tumors and other diseases of the central nervous system. These results will be further validated in clinical Trials.
SCIDOT-08. CHILDREN’S BRAIN TUMOUR DRUG DELIVERY CONSORTIUM (CBTDDC)
Authors: Ruman Rahman, Emma Campbell, Henry Brem, Monica Pearl, Jordan Green, Miroslaw Janowski, Piotr Walczak, Betty Tyler, Katherine Warren, Will Singleton, Alexander Mullen, Marie Boyd, Gareth Veal, Darren Hargrave, Dannis van Vuurden, Steven Powell, Giuseppe Battaglia, Igor Vivanco, Khuloud Al-Jamal, David Walker
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The brain tumour community has seen significant progress in the discovery of new therapeutic targets and anticancer drugs. Unfortunately, advances in how to deliver drugs to the brain lag behind. The blood-brain barrier restricts the entry of many small-molecule drugs and nearly all large molecule drugs that have been developed to treat brain disorders. METHODS Following an international CNS drug delivery workshop in 2016, we were awarded funding from Children with Cancer UK to launch the Children’s Brain Tumour Drug Delivery Consortium (CBTDDC; www.cbtddc.org; @cbtddc). RESULTS The CBTDDC launched in 2017 (in Europe and the US) to raise awareness of the challenge of drug delivery in childhood brain tumours, and to initiate and strengthen research collaborations to accelerate the development of drug delivery systems. We ran a Workshop on Drug Delivery to the Brain, attracting 52 delegates from the UK, Belgium, Spain and Portugal. We liaised with UK-based funders over the drug delivery agenda, and with UK policy makers. In the US, we jointly organised the SIGN2019 meeting and we are currently liaising with the leads of Project ‘All In’ DIPG about how we can lend our support to this project. As of June 2019, 150 individuals have registered with the consortium, representing researchers, clinicians, charities, patient groups and industry. These stakeholders represent 70 research institutions, covering 15 countries (France, UK, Italy, Sweden, The Netherlands, USA, Greece, Germany, Belgium, Cuba, Denmark, Spain, Portugal, Israel and Egypt). We host a freely accessible online collaborative research database, containing the details of over 70 researchers. CONCLUSION We believe that collaboration between clinicians and multi-disciplinary researchers is vital to solving the brain tumour drug delivery challenge. We hope to raise awareness of the CBTDDC, and to extend our invitation for collaborators to join the consortium, through SCIDOT’s unrivalled drug delivery platform.
Abstract 13459: Cardiac Malfunction Assessed by Dobutamine Stress Echocardiography in Dysmetabolic Nonhuman Primates With Proteinuria
Authors: Johannes Wikström, Yongqiang Liu, Carl Whatling, Elyse Di Marco, Li-ming Gan, Yanqin Ji, Yong-Fu Xiao, Yixin (Jim) Wang
Journal: Circulation (2018)

Introduction: Intervention studies in human like species such as nonhuman primates (NHPs), will strengthen target validation and reduce risk of attrition in late stage drug development. Echocardiog...
INNV-01. KETOGENIC METABOLIC THERAPY SIGNIFICANTLY IMPROVES RADIOGRAPHIC AND CLINICAL RESPONSE TO SALVAGE TEMAZOLAMIDE IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS
Authors: Kris Smith
Journal: Neuro-Oncology (2019)

Abstract Ketogenic Metabolic Therapy (KMT), by the proposed Warburg effect, has been shown in animal studies to augment responses to chemotherapy in laboratory models of high grade gliomas. Anecdotal responses in human patients have also been reported. We advised patients in our clinic to adhere to a low-carbohydrate, high-fat diet to obtain a state of nutritional ketosis while undergoing temazolamide (TMZ) chemotherapy for recurrent high-grade gliomas. A registered dietitian, specifically trained in KMT was utilized as a consultant for all of these patients. Blood ketone levels were checked frequently to assure ketone levels above 0.5 mmol/L. Nine patients have documented a near-continuous state of ketosis for at least 3 months while on TMZ therapy and have shown significant radiographic resolution of recurrent disease based on serial high resolution MRI surveillance imaging. All of these patients had shown progressive recurrent disease on serial MRI imaging prior to initiation of KMT. 4 of the 9 patients obtained a complete response, while the other 5 experienced a partial response. None of the patients failed to show any improvement in their imaging follow-up while on KMT. Three of the 9 patients also had salvage radiation therapy to some local area of recurrence prior to initiating KMT. There were no adverse effects related to the KMT diet. Most patients stated that they felt an overall improvement in quality of life while on the diet and embraced the diet as a means of feeling more in control of their disease. The diet was well tolerated and not felt to be a hardship or burdensome after an initial learning curve transition period was overcome. Based on these highly positive preliminary results, we suggest that KMT be included in larger prospective randomized trials for up-front and recurrent high-grade glioma trials to augment standard and experimental therapies.
Comparison of CT and PET-Based Assessments per Lugano Criteria in FDG-Avid Lymphoma- a Retrospective Analysis of Independent Review Assessments
Authors: Jayant Narang, Surabhi Bajpai, Rudresh Rajnikant Jarecha, Sayali Karve, Katarina Ludajic, Manish Sharma, Shweta Narang, Michael O'Connor
Journal: Blood (2019)
Treatment of Delayed Hemolytic Transfusion Reactions in Sickle Cell Disease Patients By an Anti-C5 Antibody
Authors: Aline Floch, Alexandre Morel, Fabian Zanchetta-Balint, Catherine Cordonnier-Jourdin, Slimane Allali, Maximilien Grall, Ghislaine Ithier, Benjamin Carpentier, Sadaf Pakdaman, Jean-Claude Merle, Radjiv Goulabchand, Tackwa Khalifeh, Ana Berceanu, Christelle Chantalat-Auger, Véronique Frémeaux-Bacchi, Marc Michel, Armand Mekontso-Dessap, Anoosha Habibi, France Pirenne, Pablo Bartolucci
Journal: Blood (2019)
Efficacy of Artesunate for Treatment of Cytomegalovirus Reactivations in Allogeneic Haematopoietic Stem Cell Transplant Recipients Who Are Intolerant/Unsuitable for Ganciclovir Therapy
Authors: Ramnath K Shenoy, Anant Gokarn, Anup Toshniwal, Siddhesh Arun Kalantri, Akanksha Chichra, Sachin Punatar, Avinash Bonda, Lingaraj Nayak, Libin J Mathew, Vivek Bhat, Sanjay Biswas, Rohini Kelkar, Navin Khattry
Journal: Blood (2019)